Genetic Variant NM_174952.3:c.1121C>T (chr4-97840856-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_174952.3(STPG2):c.1121C>T(p.Pro374Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,611,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

STPG2
NM_174952.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38

Variant links:

Genes affected

STPG2 (HGNC:28712): (sperm tail PG-rich repeat containing 2)

STPG2 links:

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
STPG2	NM_174952.3 link	c.1121C>T	p.Pro374Leu	missense_variant	Exon 9 of 11	ENST00000295268.4	NP_777612.1	Q8N412

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STPG2	ENST00000295268.4 link	c.1121C>T	p.Pro374Leu	missense_variant	Exon 9 of 11	1	NM_174952.3	ENSP00000295268.3	Q8N412
STPG2	ENST00000522676.5 link	c.263C>T	p.Pro88Leu	missense_variant	Exon 3 of 5	1		ENSP00000428346.1	H0YAZ7
STPG2	ENST00000506482.1 link	n.152+52196C>T		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250400

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135322

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460480

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726550

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151404

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73950

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 10, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1121C>T (p.P374L) alteration is located in exon 9 (coding exon 9) of the STPG2 gene. This alteration results from a C to T substitution at nucleotide position 1121, causing the proline (P) at amino acid position 374 to be replaced by a leucine (L). 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

.;T

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.7

.;M

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.5

D;D

REVEL

Benign

0.27

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.62

MutPred

0.43

.;Loss of catalytic residue at P373 (P = 0.016);

MVP

0.45

MPC

0.11

ClinPred

0.99

GERP RS

5.5

Varity_R

0.70

gMVP

0.49

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