rs760582733

chrX-83508677-C-AchrX-83508677-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.353C>A(p.Pro118Gln) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P118L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: POU3F4 NM_000307.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63

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=0.18841437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU3F4	NM_000307.5	c.353C>A	p.Pro118Gln	missense_variant	1/1	ENST00000644024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU3F4	ENST00000644024.2	c.353C>A	p.Pro118Gln	missense_variant	1/1		NM_000307.5	P1
	ENST00000625081.1	n.538G>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000560 AC: 1 AN: 178490 Hom.: 0 AF XY: 0.0000154 AC XY: 1 AN XY: 64918

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000367

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000182 AC: 2 AN: 1097849 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 2 AN XY: 363273

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	18
Dann	Uncertain	0.99
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.31	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.28	N;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.0080	D;.
Sift4G	Benign	0.14	T;.
Vest4		0.24
MutPred		0.22		Loss of glycosylation at P118 (P = 0.0302);Loss of glycosylation at P118 (P = 0.0302);
MVP		0.89
MPC		1.1
ClinPred		0.24	T
GERP RS		4.6
gMVP		0.48

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: rs760582733; hg19: chrX-82763685;