rs3741311

chr11-118118839-G-Achr11-118118839-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019894.4(TMPRSS4):c.*926G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 985,100 control chromosomes in the GnomAD database, including 179,742 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.61 (28512 hom., cov: 31)
  • Exomes 𝑓: 0.60 (151230 hom.)
• Consequence: TMPRSS4 NM_019894.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMPRSS4	NM_019894.4	c.*926G>A		3_prime_UTR_variant	13/13	ENST00000437212.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMPRSS4	ENST00000437212.8	c.*926G>A		3_prime_UTR_variant	13/13	1	NM_019894.4	A1
TMPRSS4	ENST00000534111.5	c.*926G>A		3_prime_UTR_variant	13/13	2		A1
TMPRSS4	ENST00000616579.4	c.*926G>A		3_prime_UTR_variant	12/12	5

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92945 AN: 151888 Hom.: 28473 Cov.: 31

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.607

GnomAD4 exome AF: 0.602 AC: 501685 AN: 833094 Hom.: 151230 Cov.: 40 AF XY: 0.601 AC XY: 231267 AN XY: 384706

Gnomad4 AFR exome AF: 0.628

Gnomad4 AMR exome AF: 0.657

Gnomad4 ASJ exome AF: 0.602

Gnomad4 EAS exome AF: 0.683

Gnomad4 SAS exome AF: 0.728

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.598

Gnomad4 OTH exome AF: 0.611

GnomAD4 genome AF: 0.612 AC: 93043 AN: 152006 Hom.: 28512 Cov.: 31 AF XY: 0.616 AC XY: 45757 AN XY: 74310

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.610

Alfa AF: 0.603 Hom.: 56988

Bravo AF: 0.612

Asia WGS AF: 0.701 AC: 2437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.74
Dann	Benign	0.43

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: rs3741311; hg19: chr11-117989554;