chrX-155065917-C-T

Position:

chrX-155065917-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001018025.4(MTCP1):c.94G>A(p.Val32Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,208,857 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

MTCP1
NM_001018025.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

MTCP1 (HGNC:7423): (mature T cell proliferation 1) This gene was identified by involvement in some t(X;14) translocations associated with mature T-cell proliferations. This region has a complex gene structure, with a common promoter and 5' exon spliced to two different sets of 3' exons that encode two different proteins. This gene represents the upstream 13 kDa protein that is a member of the TCL1 family. This protein may be involved in leukemogenesis. [provided by RefSeq, Mar 2009]

MTCP1 links:

CMC4 (HGNC:35428): (C-X9-C motif containing 4) This gene was identified by involvement in some t(X;14) translocations associated with mature T-cell proliferations. This region has a complex gene structure, with a common promoter and 5' exon spliced to two different sets of 3' exons that encode two different proteins. This gene represents the downstream 8 kDa protein that localizes to mitochondria.[provided by RefSeq, Mar 2009]

CMC4 links:

MTCP1 (HGNC:):

MTCP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07826325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTCP1	NM_001018025.4 linkuse as main transcript	c.94G>A	p.Val32Ile	missense_variant	2/5	ENST00000369476.8	NP_001018025.1	P56278-1
CMC4	NM_001018024.3 linkuse as main transcript	c.-10-1884G>A		intron_variant		ENST00000369484.8	NP_001018024.1	P56277-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTCP1	ENST00000369476.8 linkuse as main transcript	c.94G>A	p.Val32Ile	missense_variant	2/5	3	NM_001018025.4	ENSP00000358488.3		P56278-1
CMC4	ENST00000369484.8 linkuse as main transcript	c.-10-1884G>A		intron_variant		1	NM_001018024.3	ENSP00000358496.3		P56277-1

Frequencies

GnomAD3 genomes

AF:

0.00000889

AC:

AN:

112520

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34672

show subpopulations

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000166

AC:

AN:

181159

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67025

show subpopulations

Gnomad AFR exome

AF:

0.0000807

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000529

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1096337

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

361723

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000889

AC:

AN:

112520

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34672

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2024

The c.94G>A (p.V32I) alteration is located in exon 2 (coding exon 1) of the MTCP1 gene. This alteration results from a G to A substitution at nucleotide position 94, causing the valine (V) at amino acid position 32 to be replaced by an isoleucine (I). 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

0.076

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.020

T;T

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.078

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.64

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.10

N;N

REVEL

Benign

0.055

Sift

Benign

0.81

T;T

Sift4G

Benign

0.87

T;T

Polyphen

0.0010

B;B

Vest4

0.040

MutPred

0.58

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.46

MPC

0.97

ClinPred

0.024

GERP RS

3.8

Varity_R

0.19

gMVP

0.60

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over