rs689264

Positions:

• chr11-118086543-C-T

Variant summary

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

The NM_019894.4(TMPRSS4):​c.4-8273C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,236 control chromosomes in the GnomAD database, including 1,617 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 0.13 (1617 hom., cov: 33)
• Consequence: TMPRSS4 NM_019894.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422

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]

SMIM35 (HGNC:44179): (small integral membrane protein 35) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS4	NM_019894.4	c.4-8273C>T		intron_variant		ENST00000437212.8	NP_063947.2
SMIM35	NM_001394165.1	c.7+208G>A		intron_variant		ENST00000689828.1	NP_001381094.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS4	ENST00000437212.8	c.4-8273C>T		intron_variant		1	NM_019894.4	ENSP00000416037.3
SMIM35	ENST00000689828.1	c.7+208G>A		intron_variant			NM_001394165.1	ENSP00000509259.1
TMPRSS4	ENST00000522824.5	c.4-8273C>T		intron_variant		1		ENSP00000430547.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19507 AN: 152118 Hom.: 1610 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0469

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.109

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.128 AC: 19553 AN: 152236 Hom.: 1617 Cov.: 33 AF XY: 0.130 AC XY: 9712 AN XY: 74434

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0469

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0750

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0857 Hom.: 895

Bravo AF: 0.134

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.56

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: rs689264; hg19: chr11-117957258;