Genetic Variant NM_001199013.2:c.898G>A (chr1-24360881-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001199013.2(STPG1):c.898G>A(p.Ala300Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00668 in 1,613,472 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 54 hom. )

Consequence

STPG1
NM_001199013.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.01

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]

STPG1 links:

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]

GRHL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004768133).

BP6

Variant 1-24360881-C-T is Benign according to our data. Variant chr1-24360881-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3387871.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STPG1	NM_001199013.2 link	c.898G>A	p.Ala300Thr	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
STPG1	ENST00000337248.9 link	c.898G>A	p.Ala300Thr	missense_variant	Exon 8 of 9	5	NM_001199013.2	ENSP00000337461.4		Q5TH74-1

Frequencies

GnomAD3 genomes

AF:

0.00415

AC:

632

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00736

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00375

AC:

937

AN:

249636

Hom.:

AF XY:

0.00383

AC XY:

518

AN XY:

135072

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.00259

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00158

Gnomad NFE exome

AF:

0.00656

Gnomad OTH exome

AF:

0.00444

GnomAD4 exome

AF:

0.00695

AC:

10150

AN:

1461166

Hom.:

Cov.:

AF XY:

0.00666

AC XY:

4844

AN XY:

726838

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00214

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00101

Gnomad4 FIN exome

AF:

0.00195

Gnomad4 NFE exome

AF:

0.00846

Gnomad4 OTH exome

AF:

0.00616

GnomAD4 genome

AF:

0.00415

AC:

632

AN:

152306

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

266

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00736

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00597

Hom.:

Bravo

AF:

0.00432

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.00348

AC:

423

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00650

EpiControl

AF:

0.00582

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

STPG1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.4

DANN

Benign

0.52

DEOGEN2

Benign

0.0022

T;T;.

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.55

.;T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.16

N;N;N

REVEL

Benign

0.036

Sift

Benign

0.53

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.15

B;B;B

Vest4

0.19

MVP

0.088

MPC

0.18

ClinPred

0.0012

GERP RS

2.2

Varity_R

0.025

gMVP

0.19

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over