rs398124631

Positions:

• chr5-146340306-CGCTATCCA-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_002700.3(POU4F3):​c.882_889del​(p.Ile295ThrfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: POU4F3 NM_002700.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.88

Genes affected

POU4F3 (HGNC:9220): (POU class 4 homeobox 3) This gene encodes a member of the POU-domain family of transcription factors. POU-domain proteins have been observed to play important roles in control of cell identity in several systems. This protein is found in the retina and may play a role in determining or maintaining the identities of a small subset of visual system neurons. Defects in this gene are the cause of non-syndromic sensorineural deafness autosomal dominant type 15. [provided by RefSeq, Mar 2009]

LOC127814297 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 4 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-146340306-CGCTATCCA-C is Pathogenic according to our data. Variant chr5-146340306-CGCTATCCA-C is described in ClinVar as [Pathogenic]. Clinvar id is 7078.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-146340306-CGCTATCCA-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU4F3	NM_002700.3	c.882_889del	p.Ile295ThrfsTer5	frameshift_variant	2/2	ENST00000646991.2	NP_002691.1
LOC127814297	NM_001414499.1	c.*751_*758del		3_prime_UTR_variant	20/20		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU4F3	ENST00000646991.2	c.882_889del	p.Ile295ThrfsTer5	frameshift_variant	2/2		NM_002700.3	ENSP00000495718	P1
	ENST00000515598.1	n.404-33038_404-33031del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 15 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2003

- -

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: rs398124631; hg19: chr5-145719869;