rs891969

Positions:

• chr5-146340674-G-A
• chr5-146340674-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002700.3(POU4F3):​c.*230G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 603,634 control chromosomes in the GnomAD database, including 12,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3056 hom., cov: 33)
  • Exomes 𝑓: 0.20 (9617 hom.)
• Consequence: POU4F3 NM_002700.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.923

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]

LOC127814297 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 5-146340674-G-A is Benign according to our data. Variant chr5-146340674-G-A is described in ClinVar as [Benign]. Clinvar id is 1283952.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU4F3	NM_002700.3	c.*230G>A		3_prime_UTR_variant	2/2	ENST00000646991.2	NP_002691.1
LOC127814297	NM_001414499.1	c.*1116G>A		3_prime_UTR_variant	20/20		NP_001401428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU4F3	ENST00000646991.2	c.*230G>A		3_prime_UTR_variant	2/2		NM_002700.3	ENSP00000495718.1
ENSG00000250025	ENST00000515598.1	n.404-33398C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29568 AN: 151964 Hom.: 3054 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.202 AC: 91389 AN: 451552 Hom.: 9617 Cov.: 5 AF XY: 0.198 AC XY: 47356 AN XY: 239102

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.198

GnomAD4 genome AF: 0.195 AC: 29587 AN: 152082 Hom.: 3056 Cov.: 33 AF XY: 0.196 AC XY: 14559 AN XY: 74332

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.179

Alfa AF: 0.203 Hom.: 401

Bravo AF: 0.189

Asia WGS AF: 0.180 AC: 628 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.5
DANN	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs891969; hg19: chr5-145720237; COSMIC: COSV57942832; COSMIC: COSV57942832;