11-117913874-T-C

Variant names:

• chr11-117913874-T-C
• rs768279245
• NM_001077263.3:c.712A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001077263.3(TMPRSS13):​c.712A>G​(p.Ile238Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: TMPRSS13 NM_001077263.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.85

Genes affected

TMPRSS13 (HGNC:29808): (transmembrane serine protease 13) This gene encodes a member of the type II transmembrane serine protease family. The encoded protein contains a type II transmembrane domain, a receptor class A domain, a scavenger receptor cysteine-rich domain and a protease domain. Transmembrane serine proteases are regulated by protease inhibitors and known to function in development, homeostasis, infection, and tumorigenesis. This protein facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. [provided by RefSeq, Aug 2021]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.018677324).
• BP6: Variant 11-117913874-T-C is Benign according to our data. Variant chr11-117913874-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3179893.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS13	NM_001077263.3	c.712A>G	p.Ile238Val	missense_variant	Exon 5 of 13	ENST00000524993.6	NP_001070731.1
TMPRSS13	NM_001244995.2	c.712A>G	p.Ile238Val	missense_variant	Exon 5 of 13		NP_001231924.1
TMPRSS13	NM_001206789.2	c.607A>G	p.Ile203Val	missense_variant	Exon 4 of 12		NP_001193718.1
TMPRSS13	NM_001206790.2	c.712A>G	p.Ile238Val	missense_variant	Exon 5 of 9		NP_001193719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS13	ENST00000524993.6	c.712A>G	p.Ile238Val	missense_variant	Exon 5 of 13	1	NM_001077263.3	ENSP00000434279.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.0000401 AC: 10 AN: 249554 Hom.: 0 AF XY: 0.0000369 AC XY: 5 AN XY: 135396

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000280 AC: 41 AN: 1461766 Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22 AN XY: 727190

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74312

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000479

Alfa AF: 0.0000605 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000248 AC: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 29, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.41
DEOGEN2	Benign	0.0015	.;T;.;T;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.68	T;T;T;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.019	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.5	.;.;N;.;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.48	N;N;N;N;N
REVEL	Benign	0.032
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0010	.;B;.;.;.
Vest4		0.052
MVP		0.33
MPC		0.19
ClinPred		0.025	T
GERP RS		2.9
gMVP		0.20

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

Other links and lift over

dbSNP: rs768279245; hg19: chr11-117784589;