5-146339182-C-G

Variant names:

• chr5-146339182-C-G
• NM_002700.3:c.70C>G

Variant summary

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

The NM_002700.3(POU4F3):​c.70C>G​(p.Leu24Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: POU4F3 NM_002700.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14

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]

ENSG00000275740 (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=0.24352625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU4F3	NM_002700.3	c.70C>G	p.Leu24Val	missense_variant	Exon 1 of 2	ENST00000646991.2	NP_002691.1
LOC127814297	NM_001414499.1	c.2903C>G	p.Ser968Cys	missense_variant	Exon 19 of 20		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU4F3	ENST00000646991.2	c.70C>G	p.Leu24Val	missense_variant	Exon 1 of 2		NM_002700.3	ENSP00000495718.1
ENSG00000275740	ENST00000506502.2	c.3026C>G	p.Ser1009Cys	missense_variant	Exon 20 of 20	5		ENSP00000475384.1
ENSG00000250025	ENST00000515598.1	n.404-31906G>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.89	.;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.14
Sift	Uncertain	0.013	.;D
Sift4G	Benign	0.095	.;T
Polyphen		0.64	P;P
Vest4		0.61
MutPred		0.18		Loss of stability (P = 0.0789);Loss of stability (P = 0.0789);
MVP		0.41
MPC		0.77
ClinPred		0.79	D
GERP RS		4.5
Varity_R		0.27
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-145718745;