4-67914644-T-C

Variant names:

• chr4-67914644-T-C
• rs531482712
• NM_001114387.2:c.1039A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001114387.2(TMPRSS11A):​c.1039A>G​(p.Ile347Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TMPRSS11A NM_001114387.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114387.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS11A	NM_001114387.2	MANE Select	c.1039A>G	p.Ile347Val	missense	Exon 9 of 10	NP_001107859.1	Q6ZMR5-2
	TMPRSS11A	NM_182606.4		c.1048A>G	p.Ile350Val	missense	Exon 9 of 10	NP_872412.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS11A	ENST00000508048.6	TSL:1 MANE Select	c.1039A>G	p.Ile347Val	missense	Exon 9 of 10	ENSP00000426911.2	Q6ZMR5-2
	UBA6-DT	ENST00000500538.7	TSL:1	n.1988-147963T>C		intron	N/A
	TMPRSS11A	ENST00000334830.11	TSL:2	c.1048A>G	p.Ile350Val	missense	Exon 9 of 10	ENSP00000334611.7	A0A0A0MR82

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251344 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461418 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727018

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000671 AC: 3 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111672

Other (OTH) AF: 0.0000331 AC: 2 AN: 60374

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74488

African (AFR) AF: 0.0000241 AC: 1 AN: 41570

American (AMR) AF: 0.000261 AC: 4 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.0000413 Hom.: 0

Bravo AF: 0.0000529

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Uncertain	0.99
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.17	D
PhyloP100		1.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.60	N
REVEL	Uncertain	0.40
Sift	Benign	0.21	T
Sift4G	Benign	0.29	T
Vest4		0.14
MutPred		0.60		Loss of catalytic residue at P352 (P = 0.0303)
MVP		0.75
MPC		0.46
ClinPred		0.55	D
GERP RS		4.7
gMVP		0.53
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs531482712; hg19: chr4-68780362;