rs1220639301

Variant names:

• chr20-45207580-A-G
• rs1220639301
• NM_003007.5:c.283A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 13/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0220
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20948881).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003007.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMG1	NM_003007.5	MANE Select	c.283A>G	p.Lys95Glu	missense	Exon 2 of 3	NP_002998.1	P04279-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMG1	ENST00000372781.4	TSL:1 MANE Select	c.283A>G	p.Lys95Glu	missense	Exon 2 of 3	ENSP00000361867.3	P04279-1
	SEMG1	ENST00000922694.1		c.283A>G	p.Lys95Glu	missense	Exon 2 of 2	ENSP00000592753.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250792 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461446 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727024

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111808

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.3
DANN	Uncertain	0.98
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.022
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.056
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.023	D
Polyphen		0.94	P
Vest4		0.20
MutPred		0.54		Loss of MoRF binding (P = 0.0011)
MVP		0.23
MPC		0.050
ClinPred		0.33	T
GERP RS		1.1
Varity_R		0.23
gMVP		0.086
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1220639301; hg19: chr20-43836221;