4-67825746-C-T

Variant names:

• chr4-67825746-C-T
• NM_004262.3:c.1081G>A

Variant summary

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

The NM_004262.3(TMPRSS11D):​c.1081G>A​(p.Val361Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMPRSS11D NM_004262.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.600

Genes affected

TMPRSS11D (HGNC:24059): (transmembrane serine protease 11D) This gene encodes a trypsin-like serine protease released from the submucosal serous glands onto mucous membrane. It is a type II integral membrane protein and has 29-38% identity in the sequence of the catalytic region with human hepsin, enteropeptidase, acrosin, and mast cell tryptase. The noncatalytic region has little similarity to other known proteins. This protein may play some biological role in the host defense system on the mucous membrane independently of or in cooperation with other substances in airway mucous or bronchial secretions. This protein facilitates entry of viruses into host cells by proteolytically cleaving and activating viral envelope glycoproteins. [provided by RefSeq, Aug 2021]

UBA6-DT (HGNC:49083): (UBA6 divergent transcript)

ACMG classification

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
TMPRSS11D	NM_004262.3	c.1081G>A	p.Val361Met	missense_variant	Exon 9 of 10	ENST00000283916.11	NP_004253.1
TMPRSS11D	XM_017008851.2	c.529G>A	p.Val177Met	missense_variant	Exon 5 of 6		XP_016864340.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS11D	ENST00000283916.11	c.1081G>A	p.Val361Met	missense_variant	Exon 9 of 10	1	NM_004262.3	ENSP00000283916.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1081G>A (p.V361M) alteration is located in exon 9 (coding exon 9) of the TMPRSS11D gene. This alteration results from a G to A substitution at nucleotide position 1081, causing the valine (V) at amino acid position 361 to be replaced by a methionine (M). 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	Benign	0.17
BayesDel_addAF	Benign	-0.0043	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	0.043	D
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.35
Sift	Benign	0.070	T
Sift4G	Uncertain	0.023	D
Polyphen		0.97	D
Vest4		0.33
MutPred		0.49		Gain of disorder (P = 0.0839);
MVP		0.86
MPC		0.46
ClinPred		0.76	D
GERP RS		4.8
Varity_R		0.071
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-68691464;