3-150927631-T-TAC

Position:

• chr3-150927631-T-TAC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_174878.3(CLRN1):​c.*304_*305insGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.024 (80 hom., cov: 0)
  • Exomes 𝑓: 0.012 (2 hom.)
• Consequence: CLRN1 NM_174878.3 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: -0.454

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 Benign. Variant got -9 ACMG points.

• BP6: Variant 3-150927631-T-TAC is Benign according to our data. Variant chr3-150927631-T-TAC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 343807.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLRN1	NM_174878.3	c.*304_*305insGT		3_prime_UTR_variant	3/3	ENST00000327047.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLRN1	ENST00000327047.6	c.*304_*305insGT		3_prime_UTR_variant	3/3	1	NM_174878.3	P1
CLRN1	ENST00000295911.6	c.342+433_342+434insGT		intron_variant		1
	ENST00000469268.1	n.235+36789_235+36790dup		intron_variant, non_coding_transcript_variant		4
CLRN1-AS1	ENST00000476886.5	n.123+75053_123+75054dup		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3600 AN: 148690 Hom.: 80 Cov.: 0

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00893

Gnomad ASJ AF: 0.00965

Gnomad EAS AF: 0.00508

Gnomad SAS AF: 0.0167

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.0258

Gnomad NFE AF: 0.00850

Gnomad OTH AF: 0.0174

GnomAD3 exomes AF: 0.0133 AC: 1325 AN: 99722 Hom.: 1 AF XY: 0.0133 AC XY: 722 AN XY: 54260

Gnomad AFR exome AF: 0.0558

Gnomad AMR exome AF: 0.00726

Gnomad ASJ exome AF: 0.00930

Gnomad EAS exome AF: 0.00523

Gnomad SAS exome AF: 0.0158

Gnomad FIN exome AF: 0.0499

Gnomad NFE exome AF: 0.00826

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.0119 AC: 3854 AN: 323720 Hom.: 2 Cov.: 0 AF XY: 0.0115 AC XY: 2082 AN XY: 180926

Gnomad4 AFR exome AF: 0.0496

Gnomad4 AMR exome AF: 0.00674

Gnomad4 ASJ exome AF: 0.00821

Gnomad4 EAS exome AF: 0.00560

Gnomad4 SAS exome AF: 0.0143

Gnomad4 FIN exome AF: 0.0474

Gnomad4 NFE exome AF: 0.00775

Gnomad4 OTH exome AF: 0.0132

GnomAD4 genome AF: 0.0243 AC: 3614 AN: 148802 Hom.: 80 Cov.: 0 AF XY: 0.0260 AC XY: 1885 AN XY: 72438

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.00886

Gnomad4 ASJ AF: 0.00965

Gnomad4 EAS AF: 0.00509

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.0504

Gnomad4 NFE AF: 0.00852

Gnomad4 OTH AF: 0.0196

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, conflicting classifications

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 26, 2019

- -

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;