Genetic Variant NM_174878.3:c.*299_*304delGTGTGT (chr3-150927631-TACACAC-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_174878.3(CLRN1):c.*299_*304delGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 472,514 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0024 ( 3 hom. )

Consequence

CLRN1
NM_174878.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 1.21

Publications

1 publications found

Variant links:

Genes affected

CLRN1 (HGNC:12605): (clarin 1) This gene encodes a protein that contains a cytosolic N-terminus, multiple helical transmembrane domains, and an endoplasmic reticulum membrane retention signal, TKGH, in the C-terminus. The encoded protein may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIIa. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

CLRN1 links:

ENSG00000260234 (HGNC:):

ENSG00000260234 links:

SIAH2-AS1 (HGNC:40526): (SIAH2 antisense RNA 1)

SIAH2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 3 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174878.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLRN1	NM_174878.3	MANE Select	c.299_304delGTGTGT	3_prime_UTR	Exon 3 of 3	NP_777367.1	P58418-3
CLRN1	NM_001195794.1		c.299_304delGTGTGT	3_prime_UTR	Exon 4 of 4	NP_001182723.1	P58418-4
CLRN1	NM_001256819.2		c.612_617delGTGTGT	3_prime_UTR	Exon 4 of 4	NP_001243748.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLRN1	ENST00000327047.6	TSL:1 MANE Select	c.299_304delGTGTGT	3_prime_UTR	Exon 3 of 3	ENSP00000322280.1	P58418-3
CLRN1	ENST00000295911.6	TSL:1	c.342+428_342+433delGTGTGT	intron	N/A	ENSP00000295911.2	P58418-1
ENSG00000260234	ENST00000562308.5	TSL:1	n.103+13945_103+13950delGTGTGT	intron	N/A	ENSP00000457487.1	H3BU62

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

255

AN:

148710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000696

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000336

Gnomad ASJ

AF:

0.00234

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000215

Gnomad FIN

AF:

0.00880

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.00174

Gnomad OTH

AF:

0.00298

GnomAD2 exomes

AF:

0.00200

AC:

199

AN:

99722

AF XY:

0.00173

show subpopulations

Gnomad AFR exome

AF:

0.000836

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00261

Gnomad EAS exome

AF:

0.00317

Gnomad FIN exome

AF:

0.00744

Gnomad NFE exome

AF:

0.00156

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00236

AC:

765

AN:

323692

Hom.:

AF XY:

0.00227

AC XY:

411

AN XY:

180966

show subpopulations

African (AFR)

AF:

0.00133

AC:

AN:

9770

American (AMR)

AF:

0.00143

AC:

AN:

26488

Ashkenazi Jewish (ASJ)

AF:

0.00316

AC:

AN:

12330

East Asian (EAS)

AF:

0.00484

AC:

AN:

13018

South Asian (SAS)

AF:

0.00128

AC:

AN:

53742

European-Finnish (FIN)

AF:

0.00799

AC:

109

AN:

13634

Middle Eastern (MID)

AF:

0.00147

AC:

AN:

1356

European-Non Finnish (NFE)

AF:

0.00224

AC:

396

AN:

176870

Other (OTH)

AF:

0.00218

AC:

AN:

16484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.426

Heterozygous variant carriers

102

136

170

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:

0.00171

AC:

255

AN:

148822

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

152

AN XY:

72452

show subpopulations

African (AFR)

AF:

0.000694

AC:

AN:

40350

American (AMR)

AF:

0.000335

AC:

AN:

14906

Ashkenazi Jewish (ASJ)

AF:

0.00234

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.000215

AC:

AN:

4656

European-Finnish (FIN)

AF:

0.00880

AC:

AN:

10108

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00174

AC:

117

AN:

67060

Other (OTH)

AF:

0.00295

AC:

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

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:

0.00585

Hom.:

963

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Retinitis pigmentosa-deafness syndrome (1)

Retinitis Pigmentosa, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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NM_174878.3:c.299_304delGTGTGT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over