Genetic Variant CLRN1:c.*297_*304dupGTGTGTGT (chr3-150927631-T-TACACACAC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_174878.3(CLRN1):c.*297_*304dupGTGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

CLRN1
NM_174878.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.454

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.297_304dupGTGTGTGT	3_prime_UTR	Exon 3 of 3	NP_777367.1	P58418-3
CLRN1	NM_001195794.1		c.297_304dupGTGTGTGT	3_prime_UTR	Exon 4 of 4	NP_001182723.1	P58418-4
CLRN1	NM_001256819.2		c.610_617dupGTGTGTGT	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.297_304dupGTGTGTGT	3_prime_UTR	Exon 3 of 3	ENSP00000322280.1	P58418-3
CLRN1	ENST00000295911.6	TSL:1	c.342+426_342+433dupGTGTGTGT	intron	N/A	ENSP00000295911.2	P58418-1
ENSG00000260234	ENST00000562308.5	TSL:1	n.103+13943_103+13950dupGTGTGTGT	intron	N/A	ENSP00000457487.1	H3BU62

Frequencies

GnomAD3 genomes

AF:

0.0000807

AC:

AN:

148724

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000672

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

324596

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

181460

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000408

AC:

AN:

9802

American (AMR)

AF:

0.0000376

AC:

AN:

26608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12336

East Asian (EAS)

AF:

0.00

AC:

AN:

13222

South Asian (SAS)

AF:

0.00

AC:

AN:

53842

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1364

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

177214

Other (OTH)

AF:

0.0000605

AC:

AN:

16524

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000113520), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.367

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:

0.0000806

AC:

AN:

148836

Hom.:

Cov.:

AF XY:

0.0000690

AC XY:

AN XY:

72460

show subpopulations

African (AFR)

AF:

0.000273

AC:

AN:

40348

American (AMR)

AF:

0.0000671

AC:

AN:

14908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3420

East Asian (EAS)

AF:

0.00

AC:

AN:

5108

South Asian (SAS)

AF:

0.00

AC:

AN:

4656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67064

Other (OTH)

AF:

0.00

AC:

AN:

2036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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:

0.00

Hom.:

963

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.45

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over