4-67929915-G-A

Position:

• chr4-67929915-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001114387.2(TMPRSS11A):​c.446C>T​(p.Ala149Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TMPRSS11A NM_001114387.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31005356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMPRSS11A	NM_001114387.2	c.446C>T	p.Ala149Val	missense_variant	5/10	ENST00000508048.6	NP_001107859.1
TMPRSS11A	NM_182606.4	c.455C>T	p.Ala152Val	missense_variant	5/10		NP_872412.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMPRSS11A	ENST00000508048.6	c.446C>T	p.Ala149Val	missense_variant	5/10	1	NM_001114387.2	ENSP00000426911	P3
UBA6-DT	ENST00000500538.7	n.1988-132692G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460944 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726746

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Sep 22, 2023

The c.455C>T (p.A152V) alteration is located in exon 5 (coding exon 5) of the TMPRSS11A gene. This alteration results from a C to T substitution at nucleotide position 455, causing the alanine (A) at amino acid position 152 to be replaced by a valine (V). 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	0.090
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.70	.;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.5	.;N;N
REVEL	Benign	0.14
Sift	Benign	0.062	.;T;T
Sift4G	Benign	0.43	T;T;T
Vest4		0.26
MutPred		0.62		.;Gain of loop (P = 0.0851);.;
MVP		0.34
MPC		0.40
ClinPred		0.91	D
GERP RS		6.0
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr4-68795633;