Variant 11-118094815-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_ModerateBA1

The NM_019894.4(TMPRSS4):c.4-1A>G variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,609,458 control chromosomes in the GnomAD database, including 114,738 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7958 hom., cov: 32)

Exomes 𝑓: 0.38 ( 106780 hom. )

Consequence

TMPRSS4
NM_019894.4 splice_acceptor, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0240

Variant links:

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 links:

TMPRSS4 (HGNC:):

TMPRSS4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.029680366 fraction of the gene. Cryptic splice site detected, with MaxEntScore 9.6, offset of 0 (no position change), new splice context is: actgactgtttttccttcAGtta. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS4	NM_019894.4 linkuse as main transcript	c.4-1A>G		splice_acceptor_variant, intron_variant		ENST00000437212.8	NP_063947.2	Q9NRS4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS4	ENST00000437212.8 linkuse as main transcript	c.4-1A>G		splice_acceptor_variant, intron_variant		1	NM_019894.4	ENSP00000416037.3		Q9NRS4-1
TMPRSS4	ENST00000522824.5 linkuse as main transcript	c.4-1A>G		splice_acceptor_variant, intron_variant		1		ENSP00000430547.1		Q9NRS4-2

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45400

AN:

151896

Hom.:

7953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.372

Gnomad EAS

AF:

0.374

Gnomad SAS

AF:

0.488

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.303

GnomAD3 exomes

AF:

0.378

AC:

92629

AN:

245266

Hom.:

18597

AF XY:

0.383

AC XY:

50685

AN XY:

132368

show subpopulations

Gnomad AFR exome

AF:

0.0903

Gnomad AMR exome

AF:

0.480

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.363

Gnomad SAS exome

AF:

0.484

Gnomad FIN exome

AF:

0.357

Gnomad NFE exome

AF:

0.367

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.377

AC:

549654

AN:

1457444

Hom.:

106780

Cov.:

AF XY:

0.380

AC XY:

275530

AN XY:

724652

show subpopulations

Gnomad4 AFR exome

AF:

0.0895

Gnomad4 AMR exome

AF:

0.469

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.402

Gnomad4 SAS exome

AF:

0.484

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.346

GnomAD4 genome

AF:

0.299

AC:

45409

AN:

152014

Hom.:

7958

Cov.:

AF XY:

0.302

AC XY:

22446

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.370

Gnomad4 ASJ

AF:

0.372

Gnomad4 EAS

AF:

0.373

Gnomad4 SAS

AF:

0.489

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.372

Gnomad4 OTH

AF:

0.300

Alfa

AF:

0.359

Hom.:

17758

Bravo

AF:

0.290

TwinsUK

AF:

0.381

AC:

1411

ALSPAC

AF:

0.376

AC:

1451

ESP6500AA

AF:

0.110

AC:

485

ESP6500EA

AF:

0.367

AC:

3154

ExAC

AF:

0.370

AC:

44868

Asia WGS

AF:

0.374

AC:

1296

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.77

Eigen

Uncertain

0.25

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.079

GERP RS

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over