Variant rs6558541 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The ENST00000636934.1(CLN8):c.645A>G(p.Pro215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 398,308 control chromosomes in the GnomAD database, including 107,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.74 ( 41419 hom., cov: 31)

Exomes 𝑓: 0.73 ( 65704 hom. )

Consequence

CLN8
ENST00000636934.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.161

Variant links:

Genes affected

CLN8 (HGNC:2079): (CLN8 transmembrane ER and ERGIC protein) This gene encodes a transmembrane protein belonging to a family of proteins containing TLC domains, which are postulated to function in lipid synthesis, transport, or sensing. The protein localizes to the endoplasmic reticulum (ER), and may recycle between the ER and ER-Golgi intermediate compartment. Mutations in this gene are associated with a disorder characterized by progressive epilepsy with cognitive disabilities (EPMR), which is a subtype of neuronal ceroid lipofuscinoses (NCL). Patients with mutations in this gene have altered levels of sphingolipid and phospholipids in the brain. [provided by RefSeq, Jul 2017]

CLN8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-1800775-A-G is Benign according to our data. Variant chr8-1800775-A-G is described in ClinVar as [Benign]. Clinvar id is 3255238.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.161 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLN8	ENST00000636934.1 linkuse as main transcript	c.645A>G	p.Pro215=	synonymous_variant	3/3	5		ENSP00000490218
CLN8	ENST00000636605.1 linkuse as main transcript	n.133A>G		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.736

AC:

111718

AN:

151870

Hom.:

41398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.790

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.632

Gnomad ASJ

AF:

0.747

Gnomad EAS

AF:

0.698

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.689

Gnomad MID

AF:

0.742

Gnomad NFE

AF:

0.744

Gnomad OTH

AF:

0.755

GnomAD4 exome

AF:

0.728

AC:

179300

AN:

246320

Hom.:

65704

Cov.:

AF XY:

0.729

AC XY:

91033

AN XY:

124812

show subpopulations

Gnomad4 AFR exome

AF:

0.800

Gnomad4 AMR exome

AF:

0.590

Gnomad4 ASJ exome

AF:

0.753

Gnomad4 EAS exome

AF:

0.630

Gnomad4 SAS exome

AF:

0.594

Gnomad4 FIN exome

AF:

0.710

Gnomad4 NFE exome

AF:

0.748

Gnomad4 OTH exome

AF:

0.736

GnomAD4 genome

AF:

0.735

AC:

111781

AN:

151988

Hom.:

41419

Cov.:

AF XY:

0.728

AC XY:

54076

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.789

Gnomad4 AMR

AF:

0.631

Gnomad4 ASJ

AF:

0.747

Gnomad4 EAS

AF:

0.698

Gnomad4 SAS

AF:

0.601

Gnomad4 FIN

AF:

0.689

Gnomad4 NFE

AF:

0.744

Gnomad4 OTH

AF:

0.756

Alfa

AF:

0.739

Hom.:

3875

Bravo

AF:

0.734

Asia WGS

AF:

0.644

AC:

2238

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 80% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 74. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

DANN

Benign

0.50

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over