NM_019894.4:c.3+4940A>G

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

2

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

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
TMPRSS4NM_019894.4 linkc.3+4940A>G intron_variant Intron 1 of 12 ENST00000437212.8 NP_063947.2 Q9NRS4-1
SMIM35NM_001394165.1 linkc.7+4506T>C intron_variant Intron 1 of 4 ENST00000689828.1 NP_001381094.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMPRSS4ENST00000437212.8 linkc.3+4940A>G intron_variant Intron 1 of 12 1 NM_019894.4 ENSP00000416037.3 Q9NRS4-1
SMIM35ENST00000689828.1 linkc.7+4506T>C intron_variant Intron 1 of 4 NM_001394165.1 ENSP00000509259.1 A0A1B0GVV1
TMPRSS4ENST00000522824.5 linkc.3+4940A>G intron_variant Intron 1 of 12 1 ENSP00000430547.1 Q9NRS4-2
TMPRSS4ENST00000714375.1 linkn.3+4940A>G intron_variant Intron 1 of 11 ENSP00000519642.1
TMPRSS4ENST00000714378.1 linkn.3+4940A>G intron_variant Intron 1 of 13 ENSP00000519645.1

Frequencies

GnomAD3 genomes
AF:
0.246
AC:
37421
AN:
151960
Hom.:
4659
Cov.:
32
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.:
32
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:
73
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
0
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
0
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
DANN
Benign
0.72
PhyloP100
-1.6
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

Publications

Other links and lift over

dbSNP: rs12279572; hg19: chr11-117952960; API