Genetic Variant SEMG1:p.Lys95Glu (chr20-45207580-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_003007.5(SEMG1):c.283A>G(p.Lys95Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,446 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: 0.0000021 ( 0 hom. )

Consequence

SEMG1
NM_003007.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0220

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]

SEMG1 links:

Genome browser will be placed here

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=0.20948881).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMG1	NM_003007.5 link	c.283A>G	p.Lys95Glu	missense_variant	Exon 2 of 3	ENST00000372781.4	NP_002998.1	P04279-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMG1	ENST00000372781.4 link	c.283A>G	p.Lys95Glu	missense_variant	Exon 2 of 3	1	NM_003007.5	ENSP00000361867.3		P04279-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250792

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461446

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.283A>G (p.K95E) alteration is located in exon 2 (coding exon 2) of the SEMG1 gene. This alteration results from a A to G substitution at nucleotide position 283, causing the lysine (K) at amino acid position 95 to be replaced by a glutamic acid (E). 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

0.22

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.3

DANN

Uncertain

0.98

DEOGEN2

Benign

0.044

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.73

M_CAP

Benign

0.0016

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.056

Sift

Uncertain

0.022

Sift4G

Uncertain

0.023

Polyphen

0.94

Vest4

0.20

MutPred

0.54

Loss of MoRF binding (P = 0.0011);

MVP

0.23

MPC

0.050

ClinPred

0.33

GERP RS

1.1

Varity_R

0.23

gMVP

0.086

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over