4-67911346-A-G

Variant names:

• chr4-67911346-A-G
• rs750435881
• NM_001114387.2:c.1253T>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.1253T>C​(p.Ile418Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,612,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TMPRSS11A NM_001114387.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.30
• 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=0.22454405).

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.1253T>C	p.Ile418Thr	missense	Exon 10 of 10	NP_001107859.1	Q6ZMR5-2
	TMPRSS11A	NM_182606.4		c.1262T>C	p.Ile421Thr	missense	Exon 10 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.1253T>C	p.Ile418Thr	missense	Exon 10 of 10	ENSP00000426911.2	Q6ZMR5-2
	UBA6-DT	ENST00000500538.7	TSL:1	n.1988-151261A>G		intron	N/A
	TMPRSS11A	ENST00000334830.11	TSL:2	c.1262T>C	p.Ile421Thr	missense	Exon 10 of 10	ENSP00000334611.7	A0A0A0MR82

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152076 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250618 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460636 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726594

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111320

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74428

African (AFR) AF: 0.00 AC: 0 AN: 41544

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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	0.33
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Benign	0.91
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.37	T
PhyloP100		4.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Vest4		0.043
MutPred		0.45		Loss of stability (P = 0.0215)
MVP		0.72
MPC		0.15
ClinPred		0.20	T
GERP RS		4.5
gMVP		0.79
Mutation Taster		=93/7	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: rs750435881; hg19: chr4-68777064;