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GeneBe

20-45207635-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003007.5(SEMG1):c.338G>A(p.Gly113Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SEMG1
NM_003007.5 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.449
Variant links:
Genes affected
SEMG1 (HGNC:10742): (semenogelin 1) The protein encoded by this gene is the predominant protein in semen. The encoded secreted protein is involved in the formation of a gel matrix that encases ejaculated spermatozoa. This preproprotein is proteolytically processed by the prostate-specific antigen (PSA) protease to generate multiple peptide products that exhibit distinct functions. One of these peptides, SgI-29, is an antimicrobial peptide with antibacterial activity. This proteolysis process also breaks down the gel matrix and allows the spermatozoa to move more freely. This gene and another similar semenogelin gene are present in a gene cluster on chromosome 20. [provided by RefSeq, Feb 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2272886).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMG1NM_003007.5 linkuse as main transcriptc.338G>A p.Gly113Asp missense_variant 2/3 ENST00000372781.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMG1ENST00000372781.4 linkuse as main transcriptc.338G>A p.Gly113Asp missense_variant 2/31 NM_003007.5 P1P04279-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461618
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727098
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 14, 2022The c.338G>A (p.G113D) alteration is located in exon 2 (coding exon 2) of the SEMG1 gene. This alteration results from a G to A substitution at nucleotide position 338, causing the glycine (G) at amino acid position 113 to be replaced by an aspartic acid (D). 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
Benign
0.15
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
Cadd
Benign
9.7
Dann
Uncertain
0.99
DEOGEN2
Benign
0.038
T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
N;N
PROVEAN
Uncertain
-3.7
D
REVEL
Benign
0.053
Sift
Benign
0.18
T
Sift4G
Benign
0.27
T
Polyphen
1.0
D
Vest4
0.20
MutPred
0.56
Loss of MoRF binding (P = 0.0387);
MVP
0.14
MPC
0.051
ClinPred
0.63
D
GERP RS
1.1
Varity_R
0.13
gMVP
0.016

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.

Other links and lift over

dbSNP: rs1983727800; hg19: chr20-43836276; API