NM_019894.4:c.*926G>A

Variant names:

• chr11-118118839-G-A
• rs3741311
• NM_019894.4:c.*926G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

TMPRSS4 Gene-Disease associations (from GenCC):

• autosomal recessive cerebral atrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019894.4. 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
	TMPRSS4	NM_019894.4	MANE Select	c.*926G>A		3_prime_UTR	Exon 13 of 13	NP_063947.2
	TMPRSS4	NM_001173551.2		c.*926G>A		3_prime_UTR	Exon 13 of 13	NP_001167022.2
	TMPRSS4	NM_001083947.2		c.*926G>A		3_prime_UTR	Exon 13 of 13	NP_001077416.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS4	ENST00000437212.8	TSL:1 MANE Select	c.*926G>A		3_prime_UTR	Exon 13 of 13	ENSP00000416037.3
	TMPRSS4	ENST00000714375.1		n.*145+1385G>A		intron	N/A	ENSP00000519642.1
	TMPRSS4	ENST00000896311.1		c.*926G>A		3_prime_UTR	Exon 13 of 13	ENSP00000566370.1

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

African (AFR) AF: 0.628 AC: 9914 AN: 15786

American (AMR) AF: 0.657 AC: 646 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 3102 AN: 5152

East Asian (EAS) AF: 0.683 AC: 2479 AN: 3630

South Asian (SAS) AF: 0.728 AC: 11991 AN: 16460

European-Finnish (FIN) AF: 0.587 AC: 162 AN: 276

Middle Eastern (MID) AF: 0.682 AC: 1105 AN: 1620

European-Non Finnish (NFE) AF: 0.598 AC: 455611 AN: 761888

Other (OTH) AF: 0.611 AC: 16675 AN: 27298

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

African (AFR) AF: 0.620 AC: 25688 AN: 41452

American (AMR) AF: 0.610 AC: 9314 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2104 AN: 3470

East Asian (EAS) AF: 0.703 AC: 3630 AN: 5166

South Asian (SAS) AF: 0.724 AC: 3487 AN: 4816

European-Finnish (FIN) AF: 0.591 AC: 6234 AN: 10550

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40518 AN: 67974

Other (OTH) AF: 0.610 AC: 1288 AN: 2110

Alfa AF: 0.605 Hom.: 120338

Bravo AF: 0.612

Asia WGS AF: 0.701 AC: 2437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.74
DANN	Benign	0.43
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

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: rs3741311; hg19: chr11-117989554;