3-150927631-TACACAC-T

Position:

• chr3-150927631-TACACAC-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000327047.6(CLRN1):​c.*299_*304del 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 ENST00000327047.6 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 1.21

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]

(HGNC:):

CLRN1-AS1 (HGNC:30895): (CLRN1 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLRN1	NM_174878.3	c.*299_*304del		3_prime_UTR_variant	3/3	ENST00000327047.6	NP_777367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLRN1	ENST00000327047.6	c.*299_*304del		3_prime_UTR_variant	3/3	1	NM_174878.3	ENSP00000322280	P1
CLRN1	ENST00000295911.6	c.342+428_342+433del		intron_variant		1		ENSP00000295911
	ENST00000469268.1	n.235+36785_235+36790del		intron_variant, non_coding_transcript_variant		4
CLRN1-AS1	ENST00000476886.5	n.123+75049_123+75054del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 255 AN: 148710 Hom.: 1 Cov.: 0

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

GnomAD3 exomes AF: 0.00200 AC: 199 AN: 99722 Hom.: 0 AF XY: 0.00173 AC XY: 94 AN XY: 54260

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 SAS exome AF: 0.00175

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.: 3 AF XY: 0.00227 AC XY: 411 AN XY: 180966

Gnomad4 AFR exome AF: 0.00133

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00316

Gnomad4 EAS exome AF: 0.00484

Gnomad4 SAS exome AF: 0.00128

Gnomad4 FIN exome AF: 0.00799

Gnomad4 NFE exome AF: 0.00224

Gnomad4 OTH exome AF: 0.00218

GnomAD4 genome AF: 0.00171 AC: 255 AN: 148822 Hom.: 1 Cov.: 0 AF XY: 0.00210 AC XY: 152 AN XY: 72452

Gnomad4 AFR AF: 0.000694

Gnomad4 AMR AF: 0.000335

Gnomad4 ASJ AF: 0.00234

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000215

Gnomad4 FIN AF: 0.00880

Gnomad4 NFE AF: 0.00174

Gnomad4 OTH AF: 0.00295

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis pigmentosa-deafness syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinitis Pigmentosa, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34027634; hg19: chr3-150645418;