2-104855600-C-G

Variant names:

• chr2-104855600-C-G
• rs756985681
• NM_006236.3:c.90C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006236.3(POU3F3):​c.90C>G​(p.Gly30Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 830,960 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. Synonymous variant affecting the same amino acid position (i.e. G30G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: POU3F3 NM_006236.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.557
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=0.557 with no splicing effect.

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.90C>G	p.Gly30Gly	synonymous	Exon 1 of 1	NP_006227.1	P20264
	POU3F3	NM_001433704.1		c.90C>G	p.Gly30Gly	synonymous	Exon 2 of 2	NP_001420633.1	P20264
	POU3F3	NR_197431.1		n.294+2031C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU3F3	ENST00000361360.4	TSL:6 MANE Select	c.90C>G	p.Gly30Gly	synonymous	Exon 1 of 1	ENSP00000355001.2	P20264
	POU3F3	ENST00000674056.1		c.90C>G	p.Gly30Gly	synonymous	Exon 4 of 4	ENSP00000501036.1	P20264
	ENSG00000269707	ENST00000598623.1	TSL:5	n.345+1768C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 830960 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 385502

African (AFR) AF: 0.0000638 AC: 1 AN: 15678

American (AMR) AF: 0.00 AC: 0 AN: 1144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5456

East Asian (EAS) AF: 0.00 AC: 0 AN: 3698

South Asian (SAS) AF: 0.00 AC: 0 AN: 18140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1632

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 757274

Other (OTH) AF: 0.00 AC: 0 AN: 27242

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		0.56
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: rs756985681; hg19: chr2-105472058;