rs1378082853

Variant names:

• chr11-118113322-G-A
• rs1378082853
• NM_019894.4:c.797G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-118113322-G-A
• chr11-118113322-G-T

Variant summary

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

The NM_019894.4(TMPRSS4):​c.797G>A​(p.Gly266Asp) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMPRSS4 NM_019894.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.232

Genes affected

TMPRSS4 (HGNC:11878): (transmembrane serine protease 4) This gene encodes a member of the serine protease family. Serine proteases are known to be involved in a variety of biological processes, whose malfunction often leads to human diseases and disorders. This gene was identified as a gene overexpressed in pancreatic carcinoma. The encoded protein is membrane bound with a N-terminal anchor sequence and a glycosylated extracellular region containing the serine protease domain. The protein has been found to promote SARS-CoV-2 entry into host cells. [provided by RefSeq, Aug 2021]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06641707).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS4	NM_019894.4	c.797G>A	p.Gly266Asp	missense_variant	Exon 9 of 13	ENST00000437212.8	NP_063947.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS4	ENST00000437212.8	c.797G>A	p.Gly266Asp	missense_variant	Exon 9 of 13	1	NM_019894.4	ENSP00000416037.3
TMPRSS4	ENST00000522824.5	c.782G>A	p.Gly261Asp	missense_variant	Exon 9 of 13	1		ENSP00000430547.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	0.0026	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	3.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.082	T;T;.;.;.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.66	T;T;T;T;T;.;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.066	T;T;T;T;T;T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.55	N;.;.;.;.;N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.7	.;.;N;N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.49	.;.;T;T;T;T;T
Sift4G	Benign	0.60	T;T;T;T;T;T;T
Polyphen		0.0050	B;.;B;B;.;B;.
Vest4		0.14
MutPred		0.43		Gain of solvent accessibility (P = 0.039);.;.;.;.;Gain of solvent accessibility (P = 0.039);.;
MVP		0.44
MPC		0.17
ClinPred		0.25	T
GERP RS		2.0
Varity_R		0.048
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1378082853; hg19: chr11-117984037;