NM_001018024.3:c.71T>C

Variant names:

• chrX-155061979-A-G
• NM_001018024.3:c.71T>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/19 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
• Publications: 0 publications found

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

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=0.10077608).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018024.3. 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
	CMC4	NM_001018024.3	MANE Select	c.71T>C	p.Met24Thr	missense	Exon 3 of 3	NP_001018024.1	P56277-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMC4	ENST00000369484.8	TSL:1 MANE Select	c.71T>C	p.Met24Thr	missense	Exon 3 of 3	ENSP00000358496.3	P56277-1
	ENSG00000288258	ENST00000504061.1	TSL:3	n.*85T>C		non_coding_transcript_exon	Exon 3 of 3	ENSP00000427132.1	A0A0G2JKI4
	ENSG00000288258	ENST00000504061.1	TSL:3	n.*85T>C		3_prime_UTR	Exon 3 of 3	ENSP00000427132.1	A0A0G2JKI4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

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	0.087
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.7
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.034
Sift	Benign	0.28	T
Sift4G	Benign	0.47	T
Polyphen		0.010	B
Vest4		0.26
MutPred		0.40		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
Mutation Taster		=84/16	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: chrX-154290254;