chr4-68461910-T-C

Variant names:

• chr4-68461910-T-C
• NM_014058.4:c.101T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014058.4(TMPRSS11E):​c.101T>C​(p.Val34Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMPRSS11E NM_014058.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.101T>C	p.Val34Ala	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.101T>C	p.Val34Ala	missense	Exon 2 of 10	ENSP00000307519.4	Q9UL52
	TMPRSS11E	ENST00000510647.1	TSL:3	n.89T>C		non_coding_transcript_exon	Exon 1 of 6	ENSP00000424109.1	H0Y9G7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.19
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.77	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.6
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.38		Gain of helix (P = 0.0696)
MVP		0.90
MPC		0.56
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.29
gMVP		0.67
Mutation Taster		=66/34	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: chr4-69327628;