chrX-83508552-GGACCAGCAGGACGT-G

Position:

• chrX-83508552-GGACCAGCAGGACGT-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_000307.5(POU3F4):​c.231_244delCCAGCAGGACGTGA​(p.Asp77fs) 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 (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: POU3F4 NM_000307.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.32

Genes affected

POU3F4 (HGNC:9217): (POU class 3 homeobox 4) This gene encodes a member of the POU-III class of neural transcription factors. This family member plays a role in inner ear development. The protein is thought to be involved in the mediation of epigenetic signals which induce striatal neuron-precursor differentiation. Mutations in this gene are associated with X chromosome-linked nonsyndromic mixed deafness. [provided by RefSeq, Dec 2012]

ENSG00000279437 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 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 5 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-83508552-GGACCAGCAGGACGT-G is Pathogenic according to our data. Variant chrX-83508552-GGACCAGCAGGACGT-G is described in ClinVar as [Pathogenic]. Clinvar id is 3601651.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU3F4	NM_000307.5	c.231_244delCCAGCAGGACGTGA	p.Asp77fs	frameshift_variant	1/1	ENST00000644024.2	NP_000298.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU3F4	ENST00000644024.2	c.231_244delCCAGCAGGACGTGA	p.Asp77fs	frameshift_variant	1/1		NM_000307.5	ENSP00000495996.1
ENSG00000279437	ENST00000625081.1	n.649_662delACGTCCTGCTGGTC		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes Cov.: 23

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

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

X-linked mixed hearing loss with perilymphatic gusher Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Institute of Rare Diseases, West China Hospital, Sichuan University

Jan 09, 2025

PVS1;PM3_Supporting;PM2_Supporting -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-82763560;