4-68461910-T-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMPRSS11E	NM_014058.4	c.101T>C	p.Val34Ala	missense_variant	Exon 2 of 10	ENST00000305363.9	NP_054777.2
TMPRSS11E	XM_047450139.1	c.-134T>C		5_prime_UTR_variant	Exon 2 of 10		XP_047306095.1
TMPRSS11E	XM_011531896.3	c.-98-4721T>C		intron_variant	Intron 1 of 8		XP_011530198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMPRSS11E	ENST00000305363.9	c.101T>C	p.Val34Ala	missense_variant	Exon 2 of 10	1	NM_014058.4	ENSP00000307519.4
TMPRSS11E	ENST00000510647.1	n.89T>C		non_coding_transcript_exon_variant	Exon 1 of 6	3		ENSP00000424109.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.101T>C (p.V34A) alteration is located in exon 2 (coding exon 2) of the TMPRSS11E gene. This alteration results from a T to C substitution at nucleotide position 101, causing the valine (V) at amino acid position 34 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-69327628;