chr1-167399272-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002697.4(POU2F1):​c.1356C>G​(p.Asn452Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

POU2F1
NM_002697.4 missense

Scores

15
3
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64
Variant links:
Genes affected
POU2F1 (HGNC:9212): (POU class 2 homeobox 1) The OCT1 transcription factor was among the first identified members of the POU transcription factor family (summarized by Sturm et al., 1993 [PubMed 8314572]). Members of this family contain the POU domain, a 160-amino acid region necessary for DNA binding to the octameric sequence ATGCAAAT.[supplied by OMIM, Jul 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
POU2F1NM_002697.4 linkuse as main transcriptc.1356C>G p.Asn452Lys missense_variant 12/16 ENST00000367866.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
POU2F1ENST00000367866.7 linkuse as main transcriptc.1356C>G p.Asn452Lys missense_variant 12/161 NM_002697.4 A1P14859-6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 21, 2024The c.1356C>G (p.N452K) alteration is located in exon 12 (coding exon 12) of the POU2F1 gene. This alteration results from a C to G substitution at nucleotide position 1356, causing the asparagine (N) at amino acid position 452 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.97
.;.;D;.;D;D
Eigen
Pathogenic
0.76
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D
M_CAP
Pathogenic
0.83
D
MetaRNN
Pathogenic
0.92
D;D;D;D;D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
4.6
.;.;H;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-5.9
D;D;D;D;.;D
REVEL
Pathogenic
0.87
Sift
Pathogenic
0.0
D;D;D;D;.;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
.;.;D;D;.;.
Vest4
0.90
MutPred
0.71
.;.;Gain of methylation at N429 (P = 4e-04);.;.;.;
MVP
0.95
MPC
0.42
ClinPred
1.0
D
GERP RS
2.7
Varity_R
0.95
gMVP
0.98

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-167368509; API