X-155061979-A-G

Position:

• chrX-155061979-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001018024.3(CMC4):​c.71T>C​(p.Met24Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: CMC4 NM_001018024.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74

Genes affected

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]

ENSG00000288258 (HGNC:):

ACMG classification

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=0.10077608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMC4	NM_001018024.3	c.71T>C	p.Met24Thr	missense_variant	3/3	ENST00000369484.8	NP_001018024.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMC4	ENST00000369484.8	c.71T>C	p.Met24Thr	missense_variant	3/3	1	NM_001018024.3	ENSP00000358496.3
ENSG00000288258	ENST00000504061.1	n.*85T>C		non_coding_transcript_exon_variant	3/3	3		ENSP00000427132.1
ENSG00000288258	ENST00000504061.1	n.*85T>C		3_prime_UTR_variant	3/3	3		ENSP00000427132.1
CMC4	ENST00000369479.1	c.71T>C	p.Met24Thr	missense_variant	3/3	3		ENSP00000358491.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.71T>C (p.M24T) alteration is located in exon 3 (coding exon 2) of the CMC4 gene. This alteration results from a T to C substitution at nucleotide position 71, causing the methionine (M) at amino acid position 24 to be replaced by a threonine (T). 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	0.087
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.024	T;T
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.54	.;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.43	N;N
REVEL	Benign	0.034
Sift	Benign	0.28	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.010	B;B
Vest4		0.26
MutPred		0.40		Loss of stability (P = 0.1492);Loss of stability (P = 0.1492);
MVP		0.048
MPC		0.55
ClinPred		0.26	T
GERP RS		1.5
Varity_R		0.12
gMVP		0.24

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: chrX-154290254;