X-155065917-C-A

Variant names:

• chrX-155065917-C-A
• rs782472203
• NM_001018025.4:c.94G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001018025.4(MTCP1):​c.94G>T​(p.Val32Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 112,520 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V32I) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
• Consequence: MTCP1 NM_001018025.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 0 publications found

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]

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]

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=0.2592919).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018025.4. 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
	MTCP1	NM_001018025.4	MANE Select	c.94G>T	p.Val32Phe	missense	Exon 2 of 5	NP_001018025.1	P56278-1
	CMC4	NM_001018024.3	MANE Select	c.-10-1884G>T		intron	N/A	NP_001018024.1	P56277-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTCP1	ENST00000369476.8	TSL:3 MANE Select	c.94G>T	p.Val32Phe	missense	Exon 2 of 5	ENSP00000358488.3	P56278-1
	CMC4	ENST00000369484.8	TSL:1 MANE Select	c.-10-1884G>T		intron	N/A	ENSP00000358496.3	P56277-1
	MTCP1	ENST00000362018.2	TSL:3	c.94G>T	p.Val32Phe	missense	Exon 2 of 5	ENSP00000355058.2	P56278-1

Frequencies

GnomAD3 genomes AF: 0.00000889 AC: 1 AN: 112520 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000323

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000889 AC: 1 AN: 112520 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34672

African (AFR) AF: 0.0000323 AC: 1 AN: 30916

American (AMR) AF: 0.00 AC: 0 AN: 10694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2653

East Asian (EAS) AF: 0.00 AC: 0 AN: 3617

South Asian (SAS) AF: 0.00 AC: 0 AN: 2750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6189

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53261

Other (OTH) AF: 0.00 AC: 0 AN: 1519

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.056	T
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.7
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.22
Sift	Benign	0.074	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.44
MutPred		0.67		Loss of sheet (P = 0.1158)
MVP		0.52
MPC		1.5
ClinPred		0.33	T
GERP RS		3.8
Varity_R		0.73
gMVP		0.94
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs782472203; hg19: chrX-154294192;