chr2-104855531-C-T

Variant names:

• chr2-104855531-C-T
• rs762770245
• NM_006236.3:c.21C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006236.3(POU3F3):​c.21C>T​(p.Asn7Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00315 in 1,045,068 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0034 (5 hom.)
• Consequence: POU3F3 NM_006236.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.748
• Publications: 1 publications found

Genes affected

POU3F3 (HGNC:9216): (POU class 3 homeobox 3) This gene encodes a POU-domain containing protein that functions as a transcription factor. The encoded protein recognizes an octamer sequence in the DNA of target genes. This protein may play a role in development of the nervous system. [provided by RefSeq, Apr 2015]

ENSG00000269707 (HGNC:):

PANTR1 (HGNC:49513): (POU3F3 adjacent non-coding transcript 1) Predicted to act upstream of or within regulation of gene expression. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 2-104855531-C-T is Benign according to our data. Variant chr2-104855531-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2651213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.748 with no splicing effect.
• BS2: High AC in GnomAd4 at 238 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU3F3	NM_006236.3	MANE Select	c.21C>T	p.Asn7Asn	synonymous	Exon 1 of 1	NP_006227.1	P20264
	POU3F3	NM_001433704.1		c.21C>T	p.Asn7Asn	synonymous	Exon 2 of 2	NP_001420633.1	P20264
	POU3F3	NR_197431.1		n.294+1962C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU3F3	ENST00000361360.4	TSL:6 MANE Select	c.21C>T	p.Asn7Asn	synonymous	Exon 1 of 1	ENSP00000355001.2	P20264
	POU3F3	ENST00000674056.1		c.21C>T	p.Asn7Asn	synonymous	Exon 4 of 4	ENSP00000501036.1	P20264
	ENSG00000269707	ENST00000598623.1	TSL:5	n.345+1699C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00168 AC: 238 AN: 141492 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000511

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00251

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: 0.00276

Gnomad OTH AF: 0.00207

GnomAD2 exomes AF: 0.00102 AC: 37 AN: 36124 AF XY: 0.000828

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00152

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00193

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00338 AC: 3054 AN: 903548 Hom.: 5 Cov.: 30 AF XY: 0.00327 AC XY: 1411 AN XY: 431484

African (AFR) AF: 0.000295 AC: 5 AN: 16972

American (AMR) AF: 0.00157 AC: 11 AN: 7012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8702

East Asian (EAS) AF: 0.00 AC: 0 AN: 4578

South Asian (SAS) AF: 0.0000974 AC: 3 AN: 30806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1890

European-Non Finnish (NFE) AF: 0.00370 AC: 2962 AN: 799762

Other (OTH) AF: 0.00243 AC: 73 AN: 29990

GnomAD4 genome AF: 0.00168 AC: 238 AN: 141520 Hom.: 0 Cov.: 23 AF XY: 0.00134 AC XY: 92 AN XY: 68658

African (AFR) AF: 0.000510 AC: 20 AN: 39204

American (AMR) AF: 0.00251 AC: 36 AN: 14362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3356

East Asian (EAS) AF: 0.00 AC: 0 AN: 4678

South Asian (SAS) AF: 0.00 AC: 0 AN: 4512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00276 AC: 178 AN: 64462

Other (OTH) AF: 0.00206 AC: 4 AN: 1946

Alfa AF: 0.00194 Hom.: 0

Bravo AF: 0.00167

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	POU3F3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs762770245; hg19: chr2-105471989;