5-146339190-T-C

Variant names:

• chr5-146339190-T-C
• rs1007939112
• ENST00000506502.2:c.3034T>C

Variant summary

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

The NM_001414499.1(LOC127814297):​c.2911T>C​(p.Trp971Arg) 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. 9/11 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: 33)
• Consequence: LOC127814297 NM_001414499.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103

Genes affected

ENSG00000275740 (HGNC:):

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]

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=0.08441317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU4F3	NM_002700.3	c.78T>C	p.Ser26Ser	synonymous_variant	Exon 1 of 2	ENST00000646991.2	NP_002691.1
LOC127814297	NM_001414499.1	c.2911T>C	p.Trp971Arg	missense_variant	Exon 19 of 20		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000275740	ENST00000506502.2	c.3034T>C	p.Trp1012Arg	missense_variant	Exon 20 of 20	5		ENSP00000475384.1
POU4F3	ENST00000646991.2	c.78T>C	p.Ser26Ser	synonymous_variant	Exon 1 of 2		NM_002700.3	ENSP00000495718.1
ENSG00000250025	ENST00000515598.1	n.404-31914A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.8
DANN	Benign	0.69
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.084	T
Vest4		0.062
MVP		0.52
GERP RS		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1007939112; hg19: chr5-145718753;