X-155061944-G-C

Variant names:

• chrX-155061944-G-C
• rs782008762
• NM_001018024.3:c.106C>G

Variant summary

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

The NM_001018024.3(CMC4):​c.106C>G​(p.Arg36Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000893 in 111,970 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. R36C) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
• Consequence: CMC4 NM_001018024.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.34
• Publications: 1 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 2 ACMG points.

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

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.106C>G	p.Arg36Gly	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.106C>G	p.Arg36Gly	missense	Exon 3 of 3	ENSP00000358496.3	P56277-1
	ENSG00000288258	ENST00000504061.1	TSL:3	n.*120C>G		non_coding_transcript_exon	Exon 3 of 3	ENSP00000427132.1	A0A0G2JKI4
	ENSG00000288258	ENST00000504061.1	TSL:3	n.*120C>G		3_prime_UTR	Exon 3 of 3	ENSP00000427132.1	A0A0G2JKI4

Frequencies

GnomAD3 genomes AF: 0.00000893 AC: 1 AN: 111970 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000325

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: 0.00000893 AC: 1 AN: 111970 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34140

African (AFR) AF: 0.0000325 AC: 1 AN: 30786

American (AMR) AF: 0.00 AC: 0 AN: 10587

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3586

South Asian (SAS) AF: 0.00 AC: 0 AN: 2699

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53191

Other (OTH) AF: 0.00 AC: 0 AN: 1512

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.62	T
PhyloP100		2.3
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.26
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.065	T
Polyphen		0.72	P
Vest4		0.60
MutPred		0.64		Loss of MoRF binding (P = 0.0226)
MVP		0.11
MPC		1.2
ClinPred		0.85	D
GERP RS		5.5
Varity_R		0.48
gMVP		0.69
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs782008762; hg19: chrX-154290219;