20-45221418-C-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_003008.3(SEMG2):c.29C>A(p.Ser10Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 0 hom. )
Consequence
SEMG2
NM_003008.3 missense
NM_003008.3 missense
Scores
3
3
13
Clinical Significance
Conservation
PhyloP100: 0.0890
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.06615946).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEMG2 | NM_003008.3 | c.29C>A | p.Ser10Tyr | missense_variant | 1/3 | ENST00000372769.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMG2 | ENST00000372769.4 | c.29C>A | p.Ser10Tyr | missense_variant | 1/3 | 1 | NM_003008.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000414 AC: 63AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251428Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135896
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GnomAD4 exome AF: 0.0000540 AC: 79AN: 1461838Hom.: 0 Cov.: 30 AF XY: 0.0000454 AC XY: 33AN XY: 727220
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GnomAD4 genome ? AF: 0.000414 AC: 63AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24AN XY: 74306
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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 submitter | clinical testing | Ambry Genetics | Jan 23, 2023 | The c.29C>A (p.S10Y) alteration is located in exon 1 (coding exon 1) of the SEMG2 gene. This alteration results from a C to A substitution at nucleotide position 29, causing the serine (S) at amino acid position 10 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at