3-150927631-TACACACACACACACAC-T

Variant names:

• chr3-150927631-TACACACACACACACAC-T
• rs34027634
• NM_174878.3:c.*289_*304delGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_174878.3(CLRN1):​c.*289_*304delGTGTGTGTGTGTGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000298 in 473,434 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: CLRN1 NM_174878.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

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]

ENSG00000260234 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLRN1	NM_174878.3	c.*289_*304delGTGTGTGTGTGTGTGT		3_prime_UTR_variant	Exon 3 of 3	ENST00000327047.6	NP_777367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLRN1	ENST00000327047	c.*289_*304delGTGTGTGTGTGTGTGT		3_prime_UTR_variant	Exon 3 of 3	1	NM_174878.3	ENSP00000322280.1
ENSG00000260234	ENST00000569170.5	n.160+13935_160+13950delGTGTGTGTGTGTGTGT		intron_variant	Intron 1 of 10	1		ENSP00000457784.1

Frequencies

GnomAD3 genomes AF: 0.000222 AC: 33 AN: 148726 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00150

Gnomad FIN AF: 0.0000989

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000358

Gnomad OTH AF: 0.000497

GnomAD3 exomes AF: 0.000221 AC: 22 AN: 99722 Hom.: 0 AF XY: 0.000258 AC XY: 14 AN XY: 54260

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000603

Gnomad FIN exome AF: 0.000240

Gnomad NFE exome AF: 0.000265

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000330 AC: 107 AN: 324596 Hom.: 0 AF XY: 0.000380 AC XY: 69 AN XY: 181460

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000687

Gnomad4 FIN exome AF: 0.000219

Gnomad4 NFE exome AF: 0.000339

Gnomad4 OTH exome AF: 0.000424

GnomAD4 genome AF: 0.000228 AC: 34 AN: 148838 Hom.: 0 Cov.: 0 AF XY: 0.000221 AC XY: 16 AN XY: 72460

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00172

Gnomad4 FIN AF: 0.0000989

Gnomad4 NFE AF: 0.000358

Gnomad4 OTH AF: 0.000491

ClinVar

Not reported in ClinVar

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;