NM_001114387.2:c.869A>T

Variant names:

• chr4-67919056-T-A
• rs353163
• NM_001114387.2:c.869A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001114387.2(TMPRSS11A):​c.869A>T​(p.Gln290Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMPRSS11A NM_001114387.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 50 publications found

Genes affected

TMPRSS11A (HGNC:27954): (transmembrane serine protease 11A) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30761543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS11A	NM_001114387.2	c.869A>T	p.Gln290Leu	missense_variant	Exon 8 of 10	ENST00000508048.6	NP_001107859.1
TMPRSS11A	NM_182606.4	c.878A>T	p.Gln293Leu	missense_variant	Exon 8 of 10		NP_872412.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS11A	ENST00000508048.6	c.869A>T	p.Gln290Leu	missense_variant	Exon 8 of 10	1	NM_001114387.2	ENSP00000426911.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 124023

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.96
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.17	.;T;T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-0.48	T
PhyloP100		1.0
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.8	.;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0070	.;D;D
Sift4G	Uncertain	0.0060	D;D;D
Vest4		0.25
MutPred		0.73		Gain of stability (P = 0.0144);.;.;
MVP		0.49
MPC		0.099
ClinPred		0.69	D
GERP RS		4.5
gMVP		0.79
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs353163; hg19: chr4-68784774;