4-67919056-T-G

Variant names:

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

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.869A>C​(p.Gln290Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q290L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18750444).

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.869A>C	p.Gln290Pro	missense	Exon 8 of 10	NP_001107859.1	Q6ZMR5-2
	TMPRSS11A	NM_182606.4		c.878A>C	p.Gln293Pro	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.869A>C	p.Gln290Pro	missense	Exon 8 of 10	ENSP00000426911.2	Q6ZMR5-2
	UBA6-DT	ENST00000500538.7	TSL:1	n.1988-143551T>G		intron	N/A
	TMPRSS11A	ENST00000334830.11	TSL:2	c.878A>C	p.Gln293Pro	missense	Exon 8 of 10	ENSP00000334611.7	A0A0A0MR82

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461864 Hom.: 0 Cov.: 55 AF XY: 0.00 AC XY: 0 AN XY: 727232

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 124023

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.92
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.091	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.71	T
PhyloP100		1.0
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.0050	D
Vest4		0.25
MutPred		0.60		Gain of sheet (P = 0.1945)
MVP		0.25
MPC		0.12
ClinPred		0.40	T
GERP RS		4.5
gMVP		0.79
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;