16-66696362-C-T

Variant names:

• chr16-66696362-C-T
• rs1276232184
• NM_181521.3:c.164G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_181521.3(CMTM4):​c.164G>A​(p.Gly55Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000158 in 1,269,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CMTM4 NM_181521.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01

Genes affected

CMTM4 (HGNC:19175): (CKLF like MARVEL transmembrane domain containing 4) This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and the transmembrane 4 superfamilies of signaling molecules. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 16. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMTM4	NM_181521.3	c.164G>A	p.Gly55Asp	missense_variant	Exon 1 of 4	ENST00000394106.7	NP_852662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMTM4	ENST00000394106.7	c.164G>A	p.Gly55Asp	missense_variant	Exon 1 of 4	1	NM_181521.3	ENSP00000377666.2
CMTM4	ENST00000330687.8	c.164G>A	p.Gly55Asp	missense_variant	Exon 1 of 5	1		ENSP00000333833.4
CMTM4	ENST00000563952.1	c.99+65G>A		intron_variant	Intron 1 of 3	1		ENSP00000456380.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1269402 Hom.: 0 Cov.: 31 AF XY: 0.00000320 AC XY: 2 AN XY: 625574

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: 0.0000148

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.79e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.65	T;T
M_CAP	Pathogenic	0.86	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.053	T;D
Sift4G	Benign	0.28	T;T
Polyphen		1.0	D;.
Vest4		0.59
MutPred		0.72		Loss of methylation at R56 (P = 0.0401);Loss of methylation at R56 (P = 0.0401);
MVP		0.40
MPC		1.6
ClinPred		0.98	D
GERP RS		2.3
Varity_R		0.31
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1276232184; hg19: chr16-66730265;