rs1292394947

Variant names:

• chr4-68461891-T-A
• rs1292394947
• NM_014058.4:c.82T>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014058.4(TMPRSS11E):​c.82T>A​(p.Ser28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TMPRSS11E NM_014058.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25
• Publications: 0 publications found

Genes affected

TMPRSS11E (HGNC:24465): (transmembrane serine protease 11E) Predicted to enable serine-type peptidase activity. Involved in cognition. Predicted to be integral component of plasma membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35402328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014058.4. 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
	TMPRSS11E	NM_014058.4	MANE Select	c.82T>A	p.Ser28Thr	missense	Exon 2 of 10	NP_054777.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMPRSS11E	ENST00000305363.9	TSL:1 MANE Select	c.82T>A	p.Ser28Thr	missense	Exon 2 of 10	ENSP00000307519.4	Q9UL52
	TMPRSS11E	ENST00000510647.1	TSL:3	n.70T>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000424109.1	H0Y9G7

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 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: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

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	0.094
BayesDel_addAF	Benign	0.0048	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.059
Eigen_PC	Benign	-0.068
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.23
Sift	Benign	0.13	T
Sift4G	Benign	0.20	T
Polyphen		0.75	P
Vest4		0.41
MutPred		0.36		Loss of glycosylation at S28 (P = 0.0342)
MVP		0.83
MPC		0.34
ClinPred		0.45	T
GERP RS		6.0
Varity_R		0.098
gMVP		0.45
Mutation Taster		=98/2	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: rs1292394947; hg19: chr4-69327609;