4-67919056-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001114387.2(TMPRSS11A):​c.869A>G​(p.Gln290Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,613,858 control chromosomes in the GnomAD database, including 381,635 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 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: 𝑓 0.71 (39406 hom., cov: 32)
  • Exomes 𝑓: 0.68 (342229 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0910811E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

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>G	p.Gln290Arg	missense	Exon 8 of 10	NP_001107859.1	Q6ZMR5-2
	TMPRSS11A	NM_182606.4		c.878A>G	p.Gln293Arg	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>G	p.Gln290Arg	missense	Exon 8 of 10	ENSP00000426911.2	Q6ZMR5-2
	UBA6-DT	ENST00000500538.7	TSL:1	n.1988-143551T>C		intron	N/A
	TMPRSS11A	ENST00000334830.11	TSL:2	c.878A>G	p.Gln293Arg	missense	Exon 8 of 10	ENSP00000334611.7	A0A0A0MR82

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108610 AN: 151944 Hom.: 39354 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.678

GnomAD2 exomes AF: 0.671 AC: 168689 AN: 251456 AF XY: 0.667

Gnomad AFR exome AF: 0.831

Gnomad AMR exome AF: 0.549

Gnomad ASJ exome AF: 0.612

Gnomad EAS exome AF: 0.828

Gnomad FIN exome AF: 0.664

Gnomad NFE exome AF: 0.673

Gnomad OTH exome AF: 0.648

GnomAD4 exome AF: 0.682 AC: 997570 AN: 1461796 Hom.: 342229 Cov.: 55 AF XY: 0.680 AC XY: 494758 AN XY: 727198

African (AFR) AF: 0.839 AC: 28081 AN: 33480

American (AMR) AF: 0.552 AC: 24685 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 15996 AN: 26136

East Asian (EAS) AF: 0.816 AC: 32381 AN: 39698

South Asian (SAS) AF: 0.649 AC: 56018 AN: 86258

European-Finnish (FIN) AF: 0.665 AC: 35500 AN: 53412

Middle Eastern (MID) AF: 0.557 AC: 3210 AN: 5768

European-Non Finnish (NFE) AF: 0.684 AC: 760725 AN: 1111930

Other (OTH) AF: 0.678 AC: 40974 AN: 60392

GnomAD4 genome AF: 0.715 AC: 108719 AN: 152062 Hom.: 39406 Cov.: 32 AF XY: 0.713 AC XY: 52995 AN XY: 74324

African (AFR) AF: 0.830 AC: 34453 AN: 41498

American (AMR) AF: 0.605 AC: 9230 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2131 AN: 3470

East Asian (EAS) AF: 0.823 AC: 4257 AN: 5172

South Asian (SAS) AF: 0.638 AC: 3072 AN: 4818

European-Finnish (FIN) AF: 0.672 AC: 7096 AN: 10554

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46180 AN: 67970

Other (OTH) AF: 0.679 AC: 1435 AN: 2114

Alfa AF: 0.689 Hom.: 124023

Bravo AF: 0.715

TwinsUK AF: 0.686 AC: 2542

ALSPAC AF: 0.678 AC: 2613

ESP6500AA AF: 0.836 AC: 3683

ESP6500EA AF: 0.684 AC: 5879

ExAC AF: 0.678 AC: 82282

EpiCase AF: 0.663

EpiControl AF: 0.657

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.8
DANN	Benign	0.54
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.040	T
MetaRNN	Benign	0.0000021	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.0
PrimateAI	Benign	0.46	T
PROVEAN	Benign	3.2	N
REVEL	Benign	0.25
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.073
MPC		0.10
ClinPred		0.0020	T
GERP RS		4.5
gMVP		0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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; COSMIC: COSV58360030;