dbSNP rs2233896: SEMG2:p.Gln43Lys (chr20-45221759-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003008.3(SEMG2):c.127C>A(p.Gln43Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,611,220 control chromosomes in the GnomAD database, including 24,252 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.15 ( 1811 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22441 hom. )

Consequence

SEMG2
NM_003008.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.43

Variant links:

Genes affected

SEMG2 (HGNC:10743): (semenogelin 2) The secreted protein encoded by this gene is involved in the formation of a gel matrix that encases ejaculated spermatozoa. Proteolysis by the prostate-specific antigen (PSA) breaks down the gel matrix and allows the spermatozoa to move more freely. The encoded protein is found in lesser abundance than a similar semenogelin protein. An antibacterial activity has been found for a antimicrobial peptide isolated from this protein. The genes encoding these two semenogelin proteins are found in a cluster on chromosome 20. [provided by RefSeq, Jan 2015]

SEMG2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051182806).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMG2	NM_003008.3 link	c.127C>A	p.Gln43Lys	missense_variant	Exon 2 of 3	ENST00000372769.4	NP_002999.1	Q02383

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMG2	ENST00000372769.4 link	c.127C>A	p.Gln43Lys	missense_variant	Exon 2 of 3	1	NM_003008.3	ENSP00000361855.3		Q02383

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22445

AN:

152040

Hom.:

1807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.0366

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.153

GnomAD3 exomes

AF:

0.147

AC:

36627

AN:

248474

Hom.:

3151

AF XY:

0.153

AC XY:

20571

AN XY:

134084

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0816

Gnomad ASJ exome

AF:

0.150

Gnomad EAS exome

AF:

0.0342

Gnomad SAS exome

AF:

0.158

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.180

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.171

AC:

249015

AN:

1459062

Hom.:

22441

Cov.:

AF XY:

0.170

AC XY:

123696

AN XY:

725542

show subpopulations

Gnomad4 AFR exome

AF:

0.0976

Gnomad4 AMR exome

AF:

0.0856

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.0224

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.159

GnomAD4 genome

AF:

0.148

AC:

22477

AN:

152158

Hom.:

1811

Cov.:

AF XY:

0.148

AC XY:

11036

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.155

Gnomad4 EAS

AF:

0.0364

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.164

Hom.:

3724

Bravo

AF:

0.141

TwinsUK

AF:

0.185

AC:

687

ALSPAC

AF:

0.194

AC:

749

ESP6500AA

AF:

0.107

AC:

472

ESP6500EA

AF:

0.176

AC:

1515

ExAC

AF:

0.148

AC:

18022

Asia WGS

AF:

0.0840

AC:

293

AN:

3478

EpiCase

AF:

0.177

EpiControl

AF:

0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.043

DANN

Benign

0.47

DEOGEN2

Benign

0.011

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.024

Sift

Benign

0.087

Sift4G

Benign

0.42

Polyphen

0.16

Vest4

0.060

MPC

0.085

ClinPred

0.0074

GERP RS

-3.8

Varity_R

0.099

gMVP

0.026

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over