rs139077132

Variant names:

• chr20-45207515-C-T
• rs139077132
• NM_003007.5:c.218C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003007.5(SEMG1):​c.218C>T​(p.Ala73Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,613,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: SEMG1 NM_003007.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.59
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031884044).

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.218C>T	p.Ala73Val	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.218C>T	p.Ala73Val	missense	Exon 2 of 3	ENSP00000361867.3	P04279-1
	SEMG1	ENST00000922694.1		c.218C>T	p.Ala73Val	missense	Exon 2 of 2	ENSP00000592753.1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.0000836 AC: 21 AN: 251270 AF XY: 0.0000589

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000145

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: 0.0000438 AC: 64 AN: 1461580 Hom.: 0 Cov.: 32 AF XY: 0.0000536 AC XY: 39 AN XY: 727102

African (AFR) AF: 0.000299 AC: 10 AN: 33462

American (AMR) AF: 0.000179 AC: 8 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

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

South Asian (SAS) AF: 0.000417 AC: 36 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111790

Other (OTH) AF: 0.000116 AC: 7 AN: 60384

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152110 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74290

African (AFR) AF: 0.000483 AC: 20 AN: 41428

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.000959 AC: 2 AN: 2086

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.000162

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.14
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.53
DANN	Benign	0.18
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.00058	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	L
PhyloP100		-1.6
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.0030
Sift	Benign	0.52	T
Sift4G	Benign	0.85	T
Polyphen		0.0020	B
Vest4		0.055
MVP		0.030
MPC		0.0089
ClinPred		0.0035	T
GERP RS		-3.7
PromoterAI		-0.0088	Neutral
Varity_R		0.022
gMVP		0.019
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

dbSNP: rs139077132; hg19: chr20-43836156;