3-150927631-TACACACACACACACAC-TACACACACACAC

Variant names:

• chr3-150927631-TACAC-T
• rs34027634
• NM_174878.3:c.*301_*304delGTGT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_174878.3(CLRN1):​c.*301_*304delGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 457,236 control chromosomes in the GnomAD database, including 1,686 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.10 (875 hom., cov: 0)
  • Exomes 𝑓: 0.12 (811 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: -0.0270
• Publications: 1 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: Benign. The variant received -9 ACMG points.

• BP6: Variant 3-150927631-TACAC-T is Benign according to our data. Variant chr3-150927631-TACAC-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 343810.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

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.*301_*304delGTGT		3_prime_UTR	Exon 3 of 3	NP_777367.1	P58418-3
	CLRN1	NM_001195794.1		c.*301_*304delGTGT		3_prime_UTR	Exon 4 of 4	NP_001182723.1	P58418-4
	CLRN1	NM_001256819.2		c.*614_*617delGTGT		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.*301_*304delGTGT		3_prime_UTR	Exon 3 of 3	ENSP00000322280.1	P58418-3
	CLRN1	ENST00000295911.6	TSL:1	c.342+430_342+433delGTGT		intron	N/A	ENSP00000295911.2	P58418-1
	ENSG00000260234	ENST00000562308.5	TSL:1	n.103+13947_103+13950delGTGT		intron	N/A	ENSP00000457487.1	H3BU62

Frequencies

GnomAD3 genomes AF: 0.100 AC: 14909 AN: 148482 Hom.: 873 Cov.: 0

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0679

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.0676

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0730

Gnomad OTH AF: 0.0953

GnomAD2 exomes AF: 0.146 AC: 14560 AN: 99722 AF XY: 0.140

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.100

Gnomad EAS exome AF: 0.300

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.121 AC: 37338 AN: 308642 Hom.: 811 AF XY: 0.117 AC XY: 20215 AN XY: 172620

African (AFR) AF: 0.145 AC: 1357 AN: 9376

American (AMR) AF: 0.168 AC: 4293 AN: 25558

Ashkenazi Jewish (ASJ) AF: 0.0889 AC: 1056 AN: 11882

East Asian (EAS) AF: 0.277 AC: 3496 AN: 12626

South Asian (SAS) AF: 0.0912 AC: 4697 AN: 51528

European-Finnish (FIN) AF: 0.136 AC: 1791 AN: 13156

Middle Eastern (MID) AF: 0.109 AC: 140 AN: 1282

European-Non Finnish (NFE) AF: 0.110 AC: 18484 AN: 167506

Other (OTH) AF: 0.129 AC: 2024 AN: 15728

GnomAD4 genome AF: 0.100 AC: 14928 AN: 148594 Hom.: 875 Cov.: 0 AF XY: 0.104 AC XY: 7546 AN XY: 72320

African (AFR) AF: 0.116 AC: 4675 AN: 40292

American (AMR) AF: 0.129 AC: 1917 AN: 14876

Ashkenazi Jewish (ASJ) AF: 0.0679 AC: 232 AN: 3416

East Asian (EAS) AF: 0.273 AC: 1393 AN: 5102

South Asian (SAS) AF: 0.0681 AC: 317 AN: 4654

European-Finnish (FIN) AF: 0.121 AC: 1222 AN: 10072

Middle Eastern (MID) AF: 0.104 AC: 30 AN: 288

European-Non Finnish (NFE) AF: 0.0730 AC: 4890 AN: 66964

Other (OTH) AF: 0.0968 AC: 197 AN: 2036

Alfa AF: 0.0994 Hom.: 963

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	Retinitis pigmentosa-deafness syndrome (1)
-	1	-	Retinitis Pigmentosa, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.027
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs34027634; hg19: chr3-150645418;