chr20-45221759-C-A

Position:

• chr20-45221759-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (1811 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22441 hom.)
• Consequence: SEMG2 NM_003008.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

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]

ACMG classification

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/exons	MANE	Protein	UniProt
SEMG2	NM_003008.3	c.127C>A	p.Gln43Lys	missense_variant	2/3	ENST00000372769.4	NP_002999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMG2	ENST00000372769.4	c.127C>A	p.Gln43Lys	missense_variant	2/3	1	NM_003008.3	ENSP00000361855.3

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22445 AN: 152040 Hom.: 1807 Cov.: 32

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

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.: 34 AF XY: 0.170 AC XY: 123696 AN XY: 725542

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.: 32 AF XY: 0.148 AC XY: 11036 AN XY: 74378

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	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.043
DANN	Benign	0.47
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.024
Sift	Benign	0.087	T
Sift4G	Benign	0.42	T
Polyphen		0.16	B
Vest4		0.060
MPC		0.085
ClinPred		0.0074	T
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

Other links and lift over

dbSNP: rs2233896; hg19: chr20-43850400; COSMIC: COSV65647654;