NM_006236.3:c.138C>G

Variant names:

• chr2-104855648-C-G
• rs1242875618
• NM_006236.3:c.138C>G

Variant summary

Our verdict is Likely benign. The variant received -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
• 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 -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 VariationId is 3388414.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.207 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.138C>G	p.Gly46Gly	synonymous	Exon 1 of 1	NP_006227.1	P20264
	POU3F3	NM_001433704.1		c.138C>G	p.Gly46Gly	synonymous	Exon 2 of 2	NP_001420633.1	P20264
	POU3F3	NR_197431.1		n.294+2079C>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.138C>G	p.Gly46Gly	synonymous	Exon 1 of 1	ENSP00000355001.2	P20264
	POU3F3	ENST00000674056.1		c.138C>G	p.Gly46Gly	synonymous	Exon 4 of 4	ENSP00000501036.1	P20264
	ENSG00000269707	ENST00000598623.1	TSL:5	n.345+1816C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000107 AC: 10 AN: 93448 Hom.: 0 Cov.: 24

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00226 AC: 16 AN: 7088

American (AMR) AF: 0.000574 AC: 1 AN: 1742

Ashkenazi Jewish (ASJ) AF: 0.00367 AC: 8 AN: 2178

East Asian (EAS) AF: 0.000655 AC: 2 AN: 3054

South Asian (SAS) AF: 0.00236 AC: 20 AN: 8482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 976

Middle Eastern (MID) AF: 0.00304 AC: 2 AN: 658

European-Non Finnish (NFE) AF: 0.00257 AC: 746 AN: 290198

Other (OTH) AF: 0.00300 AC: 32 AN: 10682

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000157 AC: 4 AN: 25474

American (AMR) AF: 0.000104 AC: 1 AN: 9606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2406

East Asian (EAS) AF: 0.000992 AC: 3 AN: 3024

South Asian (SAS) AF: 0.00 AC: 0 AN: 2572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 202

European-Non Finnish (NFE) AF: 0.0000451 AC: 2 AN: 44306

Other (OTH) AF: 0.00 AC: 0 AN: 1264

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00315 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		0.21
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: rs1242875618; hg19: chr2-105472106;