4-67919195-T-C

Position:

• chr4-67919195-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114387.2(TMPRSS11A):​c.730A>G​(p.Thr244Ala) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMPRSS11A NM_001114387.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2580698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS11A	NM_001114387.2	c.730A>G	p.Thr244Ala	missense_variant	8/10	ENST00000508048.6	NP_001107859.1
TMPRSS11A	NM_182606.4	c.739A>G	p.Thr247Ala	missense_variant	8/10		NP_872412.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS11A	ENST00000508048.6	c.730A>G	p.Thr244Ala	missense_variant	8/10	1	NM_001114387.2	ENSP00000426911	P3
UBA6-DT	ENST00000500538.7	n.1988-143412T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2021

The c.739A>G (p.T247A) alteration is located in exon 8 (coding exon 8) of the TMPRSS11A gene. This alteration results from a A to G substitution at nucleotide position 739, causing the threonine (T) at amino acid position 247 to be replaced by an alanine (A). 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	0.11
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	1.0
Eigen	Benign	0.043
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.52	.;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Uncertain	-0.15	T
MutationTaster	Benign	0.73	D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	.;N;N
REVEL	Benign	0.26
Sift	Benign	0.30	.;T;T
Sift4G	Benign	0.65	T;T;T
Vest4		0.12
MutPred		0.40		.;Gain of ubiquitination at K248 (P = 0.0934);.;
MVP		0.79
MPC		0.35
ClinPred		0.68	D
GERP RS		5.4
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-68784913;