Genetic Variant STPG3:p.Ser126Gly (chr9-137252108-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001004353.4(STPG3):c.376A>G(p.Ser126Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,611,880 control chromosomes in the GnomAD database, including 220 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0093 ( 9 hom., cov: 32)

Exomes 𝑓: 0.015 ( 211 hom. )

Consequence

STPG3
NM_001004353.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.115

Variant links:

Genes affected

STPG3 (HGNC:37285): (sperm-tail PG-rich repeat containing 3) Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

STPG3 links:

CIMIP2A (HGNC:33818): (ciliary microtubule inner protein 2A) Located in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

CIMIP2A links:

STPG3-AS1 (HGNC:51176): (STPG3 antisense RNA 1)

STPG3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034903288).

BP6

Variant 9-137252108-A-G is Benign according to our data. Variant chr9-137252108-A-G is described in ClinVar as [Benign]. Clinvar id is 774890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0149 (21797/1459600) while in subpopulation NFE AF= 0.0184 (20436/1111580). AF 95% confidence interval is 0.0182. There are 211 homozygotes in gnomad4_exome. There are 10544 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STPG3	NM_001004353.4 link	c.376A>G	p.Ser126Gly	missense_variant	Exon 3 of 6	ENST00000412566.6	NP_001004353.2	Q8N7X2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STPG3	ENST00000412566.6 link	c.376A>G	p.Ser126Gly	missense_variant	Exon 3 of 6	1	NM_001004353.4	ENSP00000391218.1		Q8N7X2-4

Frequencies

GnomAD3 genomes

AF:

0.00930

AC:

1415

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00350

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00861

AC:

2124

AN:

246648

Hom.:

AF XY:

0.00879

AC XY:

1179

AN XY:

134164

show subpopulations

Gnomad AFR exome

AF:

0.00318

Gnomad AMR exome

AF:

0.00480

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.000335

Gnomad SAS exome

AF:

0.00229

Gnomad FIN exome

AF:

0.00306

Gnomad NFE exome

AF:

0.0154

Gnomad OTH exome

AF:

0.00868

GnomAD4 exome

AF:

0.0149

AC:

21797

AN:

1459600

Hom.:

211

Cov.:

AF XY:

0.0145

AC XY:

10544

AN XY:

726096

show subpopulations

Gnomad4 AFR exome

AF:

0.00200

Gnomad4 AMR exome

AF:

0.00466

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00226

Gnomad4 FIN exome

AF:

0.00409

Gnomad4 NFE exome

AF:

0.0184

Gnomad4 OTH exome

AF:

0.0109

GnomAD4 genome

AF:

0.00930

AC:

1416

AN:

152280

Hom.:

Cov.:

AF XY:

0.00862

AC XY:

642

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00349

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.0155

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.0141

Hom.:

Bravo

AF:

0.00964

TwinsUK

AF:

0.0181

AC:

ALSPAC

AF:

0.0187

AC:

ESP6500AA

AF:

0.00223

AC:

ESP6500EA

AF:

0.0155

AC:

129

ExAC

AF:

0.00877

AC:

1061

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0131

EpiControl

AF:

0.0126

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.12

T;T;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.64

T;T;T;T

MetaRNN

Benign

0.0035

T;T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Uncertain

-2.6

.;D;N;.

REVEL

Benign

0.11

Sift

Benign

0.20

.;T;D;.

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

0.77

P;.;P;D

Vest4

0.35

MVP

0.49

MPC

0.096

ClinPred

0.029

GERP RS

3.8

Varity_R

0.14

gMVP

0.56

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