2-104855648-C-G

Position:

• chr2-104855648-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_006236.3(POU3F3):​c.138C>G​(p.Gly46Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POU3F3 NM_006236.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.207

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:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 2-104855648-C-G is Benign according to our data. Variant chr2-104855648-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3388414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.207 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU3F3	NM_006236.3	c.138C>G	p.Gly46Gly	synonymous_variant	1/1	ENST00000361360.4	NP_006227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU3F3	ENST00000361360.4	c.138C>G	p.Gly46Gly	synonymous_variant	1/1	6	NM_006236.3	ENSP00000355001.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 10 AN: 93448 Hom.: 0 Cov.: 24 FAILED QC

Gnomad AFR AF: 0.000157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000104

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000991

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000451

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00254 AC: 827 AN: 325058 Hom.: 0 Cov.: 4 AF XY: 0.00233 AC XY: 357 AN XY: 153292

Gnomad4 AFR exome AF: 0.00226

Gnomad4 AMR exome AF: 0.000574

Gnomad4 ASJ exome AF: 0.00367

Gnomad4 EAS exome AF: 0.000655

Gnomad4 SAS exome AF: 0.00236

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00257

Gnomad4 OTH exome AF: 0.00300

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000107 AC: 10 AN: 93492 Hom.: 0 Cov.: 24 AF XY: 0.0000439 AC XY: 2 AN XY: 45586

Gnomad4 AFR AF: 0.000157

Gnomad4 AMR AF: 0.000104

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000992

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000451

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00315 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

POU3F3: BP4, BP7, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.71

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: rs1242875618; hg19: chr2-105472106;