11-117903684-C-T

Variant names:

• chr11-117903684-C-T
• NM_001077263.3:c.1648G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001077263.3(TMPRSS13):​c.1648G>A​(p.Val550Ile) 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. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMPRSS13 NM_001077263.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.424

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 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=0.09843263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS13	NM_001077263.3	c.1648G>A	p.Val550Ile	missense_variant	Exon 12 of 13	ENST00000524993.6	NP_001070731.1
TMPRSS13	NM_001244995.2	c.1648G>A	p.Val550Ile	missense_variant	Exon 12 of 13		NP_001231924.1
TMPRSS13	NM_001206789.2	c.1543G>A	p.Val515Ile	missense_variant	Exon 11 of 12		NP_001193718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS13	ENST00000524993.6	c.1648G>A	p.Val550Ile	missense_variant	Exon 12 of 13	1	NM_001077263.3	ENSP00000434279.1
TMPRSS13	ENST00000445164.6	c.1648G>A	p.Val550Ile	missense_variant	Exon 12 of 12	1		ENSP00000394114.2
TMPRSS13	ENST00000430170.6	c.1648G>A	p.Val550Ile	missense_variant	Exon 12 of 13	1		ENSP00000387702.2
TMPRSS13	ENST00000528626.5	c.1543G>A	p.Val515Ile	missense_variant	Exon 11 of 12	1		ENSP00000435813.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1648G>A (p.V550I) alteration is located in exon 12 (coding exon 12) of the TMPRSS13 gene. This alteration results from a G to A substitution at nucleotide position 1648, causing the valine (V) at amino acid position 550 to be replaced by an isoleucine (I). 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	0.096
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.20	.;T;.;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.67	T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.098	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.19	.;.;N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.21	N;N;N;N
REVEL	Benign	0.015
Sift	Benign	0.034	D;T;T;D
Sift4G	Benign	0.16	T;T;T;T
Polyphen		0.65	.;P;.;.
Vest4		0.29
MVP		0.48
MPC		0.31
ClinPred		0.37	T
GERP RS		3.3
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-117774399;