rs145247814

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1

The NM_017882.3(CLN6):c.270C>T(p.Asn90Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

CLN6
NM_017882.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 0.123

Publications

3 publications found

Variant links:

Genes affected

CLN6 (HGNC:2077): (CLN6 transmembrane ER protein) This gene is one of eight which have been associated with neuronal ceroid lipofuscinoses (NCL). Also referred to as Batten disease, NCL comprises a class of autosomal recessive, neurodegenerative disorders affecting children. The genes responsible likely encode proteins involved in the degradation of post-translationally modified proteins in lysosomes. The primary defect in NCL disorders is thought to be associated with lysosomal storage function. [provided by RefSeq, Oct 2008]

CLN6 Gene-Disease associations (from GenCC):

ceroid lipofuscinosis, neuronal, 6A
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Myriad Women’s Health, Orphanet
ceroid lipofuscinosis, neuronal, 6B (Kufs type)
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet
neuronal ceroid lipofuscinosis
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

CLN6 links:

ENSG00000260007 (HGNC:):

ENSG00000260007 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011906147).

BP6

Variant 15-68214317-G-A is Benign according to our data. Variant chr15-68214317-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 205154.

BP7

Synonymous conserved (PhyloP=0.123 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000945 (144/152338) while in subpopulation AFR AF = 0.00322 (134/41578). AF 95% confidence interval is 0.00278. There are 0 homozygotes in GnomAd4. There are 68 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLN6	NM_017882.3 link	c.270C>T	p.Asn90Asn	synonymous_variant	Exon 3 of 7	ENST00000249806.11	NP_060352.1
CLN6	NM_001411068.1 link	c.366C>T	p.Asn122Asn	synonymous_variant	Exon 3 of 7		NP_001397997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLN6	ENST00000249806.11 link	c.270C>T	p.Asn90Asn	synonymous_variant	Exon 3 of 7	1	NM_017882.3	ENSP00000249806.5
ENSG00000260007	ENST00000562767.2 link	c.83+15185C>T		intron_variant	Intron 1 of 2	3		ENSP00000456336.1

Frequencies

GnomAD3 genomes

AF:

0.000939

AC:

143

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000219

AC:

AN:

251488

AF XY:

0.000132

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000862

AC:

126

AN:

1461550

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

33470

American (AMR)

AF:

0.000179

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1111744

Other (OTH)

AF:

0.000298

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000945

AC:

144

AN:

152338

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00322

AC:

134

AN:

41578

American (AMR)

AF:

0.000131

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68028

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000427

Hom.:

Bravo

AF:

0.000865

ESP6500AA

AF:

0.00273

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000272

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 29, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Uncertain:1

Jan 16, 2018

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

May 11, 2016

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Neuronal ceroid lipofuscinosis

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.6

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.43

M_CAP

Benign

0.0043

MetaRNN

Benign

0.012

MetaSVM

Uncertain

-0.23

PhyloP100

0.12

GERP RS

1.3

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over