4-67919195-T-C

Variant names:

• chr4-67919195-T-C
• NM_001114387.2:c.730A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/20 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
• 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 0 ACMG points.

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

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.730A>G	p.Thr244Ala	missense	Exon 8 of 10	NP_001107859.1	Q6ZMR5-2
	TMPRSS11A	NM_182606.4		c.739A>G	p.Thr247Ala	missense	Exon 8 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.730A>G	p.Thr244Ala	missense	Exon 8 of 10	ENSP00000426911.2	Q6ZMR5-2
	UBA6-DT	ENST00000500538.7	TSL:1	n.1988-143412T>C		intron	N/A
	TMPRSS11A	ENST00000334830.11	TSL:2	c.739A>G	p.Thr247Ala	missense	Exon 8 of 10	ENSP00000334611.7	A0A0A0MR82

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	0.11
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
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	-0.15	T
PhyloP100		1.5
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.26
Sift	Benign	0.30	T
Sift4G	Benign	0.65	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
Mutation Taster		=82/18	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

hg19: chr4-68784913;