NM_002701.6:c.238G>C

Variant names:

• chr6-31170383-C-G
• rs1777574425
• NM_002701.6:c.238G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002701.6(POU5F1):​c.238G>C​(p.Val80Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: POU5F1 NM_002701.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

Genes affected

POU5F1 (HGNC:9221): (POU class 5 homeobox 1) This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072601646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.238G>C	p.Val80Leu	missense_variant	Exon 1 of 5	ENST00000259915.13	NP_002692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.238G>C	p.Val80Leu	missense_variant	Exon 1 of 5	1	NM_002701.6	ENSP00000259915.7
POU5F1	ENST00000441888.7	c.-183-4336G>C		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
POU5F1	ENST00000461401.1	n.276G>C		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460366 Hom.: 0 Cov.: 37 AF XY: 0.00000275 AC XY: 2 AN XY: 726496

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.072	T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.30	N
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.073	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.89	L;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.050	N;.
REVEL	Benign	0.043
Sift	Benign	0.30	T;.
Sift4G	Benign	0.82	T;.
Polyphen		0.43	B;.
Vest4		0.11
MutPred		0.28		Loss of catalytic residue at V80 (P = 0.1538);Loss of catalytic residue at V80 (P = 0.1538);
MVP		0.48
MPC		0.55
ClinPred		0.13	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.061
gMVP		0.17

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: rs1777574425; hg19: chr6-31138160;