chr3-150927631-T-TACACACACAC

Variant names:

• chr3-150927631-T-TACACACACAC
• rs34027634
• NM_174878.3:c.*295_*304dupGTGTGTGTGT

Variant summary

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

The NM_174878.3(CLRN1):​c.*295_*304dupGTGTGTGTGT 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: CLRN1 NM_174878.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 0 publications found

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:):

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLRN1	NM_174878.3	MANE Select	c.*295_*304dupGTGTGTGTGT		3_prime_UTR	Exon 3 of 3	NP_777367.1	P58418-3
	CLRN1	NM_001195794.1		c.*295_*304dupGTGTGTGTGT		3_prime_UTR	Exon 4 of 4	NP_001182723.1	P58418-4
	CLRN1	NM_001256819.2		c.*608_*617dupGTGTGTGTGT		3_prime_UTR	Exon 4 of 4	NP_001243748.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLRN1	ENST00000327047.6	TSL:1 MANE Select	c.*295_*304dupGTGTGTGTGT		3_prime_UTR	Exon 3 of 3	ENSP00000322280.1	P58418-3
	CLRN1	ENST00000295911.6	TSL:1	c.342+424_342+433dupGTGTGTGTGT		intron	N/A	ENSP00000295911.2	P58418-1
	ENSG00000260234	ENST00000562308.5	TSL:1	n.103+13941_103+13950dupGTGTGTGTGT		intron	N/A	ENSP00000457487.1	H3BU62

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000308 AC: 1 AN: 324594 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 181460

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

African (AFR) AF: 0.00 AC: 0 AN: 9802

American (AMR) AF: 0.0000376 AC: 1 AN: 26606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12336

East Asian (EAS) AF: 0.00 AC: 0 AN: 13222

South Asian (SAS) AF: 0.00 AC: 0 AN: 53842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1364

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 177214

Other (OTH) AF: 0.00 AC: 0 AN: 16524

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

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

Other links and lift over

dbSNP: rs34027634; hg19: chr3-150645418;