rs111033345

Positions:

• chrX-83508823-C-G
• chrX-83508823-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000307.5(POU3F4):​c.499C>G​(p.Arg167Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: POU3F4 NM_000307.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.895

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13375166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU3F4	NM_000307.5	c.499C>G	p.Arg167Gly	missense_variant	1/1	ENST00000644024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU3F4	ENST00000644024.2	c.499C>G	p.Arg167Gly	missense_variant	1/1		NM_000307.5	P1
	ENST00000625081.1	n.392G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.93
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.22	N;.
REVEL	Benign	0.24
Sift	Benign	0.26	T;.
Sift4G	Benign	0.51	T;.
Vest4		0.33
MutPred		0.22		Loss of solvent accessibility (P = 0.1744);Loss of solvent accessibility (P = 0.1744);
MVP		0.85
MPC		1.3
ClinPred		0.35	T
GERP RS		2.4
gMVP		0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs111033345; hg19: chrX-82763831;