NM_003007.5:c.514A>C

Variant names:

• chr20-45207811-A-C
• NM_003007.5:c.514A>C

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.514A>C​(p.Ser172Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SEMG1 NM_003007.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.781
• 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=0.16855499).

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.514A>C	p.Ser172Arg	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.514A>C	p.Ser172Arg	missense	Exon 2 of 3	ENSP00000361867.3	P04279-1
	SEMG1	ENST00000922694.1		c.514A>C	p.Ser172Arg	missense	Exon 2 of 2	ENSP00000592753.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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	Uncertain	0.49
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.0
DANN	Benign	0.80
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.78
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.033
Sift	Benign	0.35	T
Sift4G	Benign	0.66	T
Polyphen		0.99	D
Vest4		0.19
MutPred		0.40		Gain of MoRF binding (P = 0.0121)
MVP		0.076
MPC		0.044
ClinPred		0.25	T
GERP RS		-1.5
Varity_R		0.053
gMVP		0.020
Mutation Taster		=100/0	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

hg19: chr20-43836452;