1-24360956-C-T

Variant summary

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

The NM_001199013.2(STPG1):​c.823G>A​(p.Val275Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,613,968 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

STPG1
NM_001199013.2 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25
Variant links:
Genes affected
STPG1 (HGNC:28070): (sperm tail PG-rich repeat containing 1) Involved in positive regulation of apoptotic process and positive regulation of mitochondrial membrane permeability involved in apoptotic process. Predicted to be located in mitochondrion and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
GRHL3 (HGNC:25839): (grainyhead like transcription factor 3) This gene encodes a member of the grainyhead family of transcription factors. The encoded protein may function as a transcription factor during development, and has been shown to stimulate migration of endothelial cells. Multiple transcript variants encoding distinct isoforms have been identified for this gene.[provided by RefSeq, Aug 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STPG1NM_001199013.2 linkc.823G>A p.Val275Met missense_variant Exon 8 of 9 ENST00000337248.9 NP_001185942.1 Q5TH74-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STPG1ENST00000337248.9 linkc.823G>A p.Val275Met missense_variant Exon 8 of 9 5 NM_001199013.2 ENSP00000337461.4 Q5TH74-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152230
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
251032
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135652
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000581
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461620
Hom.:
1
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727084
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000448
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152348
Hom.:
0
Cov.:
33
AF XY:
0.0000671
AC XY:
5
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000115
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.823G>A (p.V275M) alteration is located in exon 8 (coding exon 7) of the STPG1 gene. This alteration results from a G to A substitution at nucleotide position 823, causing the valine (V) at amino acid position 275 to be replaced by a methionine (M). 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
Benign
0.27
BayesDel_addAF
Uncertain
0.015
T
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.024
T;T;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.86
.;D;D
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.65
D;D;D
MetaSVM
Uncertain
-0.077
T
MutationAssessor
Uncertain
2.8
M;M;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-2.1
N;N;N
REVEL
Benign
0.20
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.016
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.62
MVP
0.45
MPC
0.65
ClinPred
0.55
D
GERP RS
5.7
Varity_R
0.33
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs528552913; hg19: chr1-24687446; API