Genetic Variant NM_019894.4:c.3+4940A>G (chr11-118082245-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_019894.4(TMPRSS4):c.3+4940A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,078 control chromosomes in the GnomAD database, including 4,662 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 0.25 ( 4662 hom., cov: 32)

Consequence

TMPRSS4
NM_019894.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

Publications

1 publications found

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:

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

SMIM35 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS4	NM_019894.4 link	c.3+4940A>G		intron_variant	Intron 1 of 12	ENST00000437212.8	NP_063947.2	Q9NRS4-1
SMIM35	NM_001394165.1 link	c.7+4506T>C		intron_variant	Intron 1 of 4	ENST00000689828.1	NP_001381094.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMPRSS4	ENST00000437212.8 link	c.3+4940A>G	intron_variant	Intron 1 of 12	1	NM_019894.4	ENSP00000416037.3	Q9NRS4-1
SMIM35	ENST00000689828.1 link	c.7+4506T>C	intron_variant	Intron 1 of 4		NM_001394165.1	ENSP00000509259.1	A0A1B0GVV1
TMPRSS4	ENST00000522824.5 link	c.3+4940A>G	intron_variant	Intron 1 of 12	1		ENSP00000430547.1	Q9NRS4-2
TMPRSS4	ENST00000714375.1 link	n.3+4940A>G	intron_variant	Intron 1 of 11			ENSP00000519642.1
TMPRSS4	ENST00000714378.1 link	n.3+4940A>G	intron_variant	Intron 1 of 13			ENSP00000519645.1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37421

AN:

151960

Hom.:

4659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.270

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

GnomAD4 genome

AF:

0.246

AC:

37426

AN:

152078

Hom.:

4662

Cov.:

AF XY:

0.247

AC XY:

18388

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.193

AC:

8008

AN:

41478

American (AMR)

AF:

0.285

AC:

4360

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

969

AN:

3470

East Asian (EAS)

AF:

0.181

AC:

938

AN:

5182

South Asian (SAS)

AF:

0.292

AC:

1407

AN:

4818

European-Finnish (FIN)

AF:

0.226

AC:

2386

AN:

10578

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.272

AC:

18498

AN:

67964

Other (OTH)

AF:

0.268

AC:

565

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1462

2924

4386

5848

7310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.256

Hom.:

815

Bravo

AF:

0.245

Asia WGS

AF:

0.232

AC:

808

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.29

(source)

DANN

Benign

0.72

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over