Genetic Variant TMPRSS5:p.Arg387Gly (chr11-113690278-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030770.4(TMPRSS5):c.1159C>G(p.Arg387Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,570,004 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

TMPRSS5
NM_030770.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

Variant links:

Genes affected

TMPRSS5 (HGNC:14908): (transmembrane serine protease 5) This gene encodes a protein that belongs to the serine protease family. Serine proteases are known to be involved in many physiological and pathological processes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

TMPRSS5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS5	NM_030770.4 link	c.1159C>G	p.Arg387Gly	missense_variant	Exon 11 of 13	ENST00000299882.11	NP_110397.2	Q9H3S3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS5	ENST00000299882.11 link	c.1159C>G	p.Arg387Gly	missense_variant	Exon 11 of 13	1	NM_030770.4	ENSP00000299882.5		Q9H3S3

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151702

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183532

Hom.:

AF XY:

0.0000102

AC XY:

AN XY:

98034

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000422

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000296

AC:

AN:

1418302

Hom.:

Cov.:

AF XY:

0.0000328

AC XY:

AN XY:

701214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000375

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.0000348

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151702

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74058

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1159C>G (p.R387G) alteration is located in exon 11 (coding exon 11) of the TMPRSS5 gene. This alteration results from a C to G substitution at nucleotide position 1159, causing the arginine (R) at amino acid position 387 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;T;T;T;.;T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.088

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.69

.;T;T;D;T;T;T;T

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.47

T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.37

MutationAssessor

Benign

-0.075

N;N;.;.;.;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.3

.;N;N;D;D;N;D;D

REVEL

Uncertain

0.50

Sift

Benign

0.10

.;T;T;T;T;T;T;T

Sift4G

Benign

0.11

.;T;T;D;T;T;T;T

Polyphen

1.0

D;D;D;D;.;.;D;.

Vest4

0.35, 0.32, 0.29, 0.31, 0.32, 0.33, 0.33

MVP

0.92

MPC

0.44

ClinPred

0.77

GERP RS

4.2

Varity_R

0.30

gMVP

0.74

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over