rs2233896

Variant names:

• chr20-45221759-C-A
• rs2233896
• NM_003008.3:c.127C>A

Your query was ambiguous. Multiple possible variants found:

• chr20-45221759-C-A
• chr20-45221759-C-G

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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	c.127C>A	p.Gln43Lys	missense_variant	Exon 2 of 3	ENST00000372769.4	NP_002999.1

Ensembl

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

GnomAD2 exomes AF: 0.147 AC: 36627 AN: 248474 AF XY: 0.153

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 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

African (AFR) AF: 0.0976 AC: 3254 AN: 33340

American (AMR) AF: 0.0856 AC: 3786 AN: 44244

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3911 AN: 26022

East Asian (EAS) AF: 0.0224 AC: 888 AN: 39696

South Asian (SAS) AF: 0.163 AC: 13867 AN: 85288

European-Finnish (FIN) AF: 0.192 AC: 10271 AN: 53384

Middle Eastern (MID) AF: 0.181 AC: 1044 AN: 5754

European-Non Finnish (NFE) AF: 0.182 AC: 202393 AN: 1111024

Other (OTH) AF: 0.159 AC: 9601 AN: 60310

GnomAD4 genome AF: 0.148 AC: 22477 AN: 152158 Hom.: 1811 Cov.: 32 AF XY: 0.148 AC XY: 11036 AN XY: 74378

African (AFR) AF: 0.105 AC: 4375 AN: 41530

American (AMR) AF: 0.127 AC: 1944 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3464

East Asian (EAS) AF: 0.0364 AC: 189 AN: 5186

South Asian (SAS) AF: 0.140 AC: 677 AN: 4822

European-Finnish (FIN) AF: 0.192 AC: 2024 AN: 10562

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12042 AN: 67984

Other (OTH) AF: 0.157 AC: 332 AN: 2114

Alfa AF: 0.164 Hom.: 7599

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
PhyloP100		-2.4
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
PromoterAI		-0.015	Neutral
Varity_R		0.099
gMVP		0.026
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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