5-146339034-C-T

Variant names:

• chr5-146339034-C-T
• rs563020230
• NM_002700.3:c.-79C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002700.3(POU4F3):​c.-79C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000315 in 1,587,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: POU4F3 NM_002700.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000184 (28/152264) while in subpopulation AFR AF= 0.000673 (28/41580). AF 95% confidence interval is 0.000478. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 28 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU4F3	NM_002700.3	c.-79C>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000646991.2	NP_002691.1
LOC127814297	NM_001414499.1	c.2824-69C>T		intron_variant	Intron 18 of 19		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU4F3	ENST00000646991	c.-79C>T		5_prime_UTR_variant	Exon 1 of 2		NM_002700.3	ENSP00000495718.1
ENSG00000275740	ENST00000506502.2	c.2947-69C>T		intron_variant	Intron 19 of 19	5		ENSP00000475384.1
ENSG00000250025	ENST00000515598.1	n.404-31758G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152146 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000153 AC: 22 AN: 1435444 Hom.: 0 Cov.: 30 AF XY: 0.0000112 AC XY: 8 AN XY: 712412

Gnomad4 AFR exome AF: 0.000518

Gnomad4 AMR exome AF: 0.0000487

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: 0.00

Gnomad4 OTH exome AF: 0.0000505

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152264 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74448

Gnomad4 AFR AF: 0.000673

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.83

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: rs563020230; hg19: chr5-145718597;