rs1409900151

Variant names:

• chr16-66604949-G-C
• rs1409900151
• NM_181553.4:c.144G>C

Variant summary

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

The NM_181553.4(CMTM3):​c.144G>C​(p.Glu48Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000598 in 1,505,412 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: CMTM3 NM_181553.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.449
• Publications: 0 publications found

Genes affected

CMTM3 (HGNC:19174): (CKLF like MARVEL transmembrane domain containing 3) 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 containing different 5' UTRs, but encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

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

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_181553.4. 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
	CMTM3	NM_181553.4	MANE Select	c.144G>C	p.Glu48Asp	missense	Exon 1 of 5	NP_853531.1	Q96MX0-1
	CMTM3	NM_001363918.2		c.144G>C	p.Glu48Asp	missense	Exon 2 of 6	NP_001350847.1	Q96MX0-1
	CMTM3	NM_001363923.2		c.144G>C	p.Glu48Asp	missense	Exon 2 of 6	NP_001350852.1	Q96MX0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTM3	ENST00000567572.6	TSL:1 MANE Select	c.144G>C	p.Glu48Asp	missense	Exon 1 of 5	ENSP00000455851.1	Q96MX0-1
	CMTM3	ENST00000361909.8	TSL:1	c.144G>C	p.Glu48Asp	missense	Exon 2 of 6	ENSP00000354579.4	Q96MX0-1
	CMTM3	ENST00000565922.1	TSL:1	c.124+20G>C		intron	N/A	ENSP00000456426.1	Q96MX0-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000517 AC: 7 AN: 1353250 Hom.: 0 Cov.: 31 AF XY: 0.00000447 AC XY: 3 AN XY: 671392

African (AFR) AF: 0.00 AC: 0 AN: 27576

American (AMR) AF: 0.00 AC: 0 AN: 30642

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23506

East Asian (EAS) AF: 0.00 AC: 0 AN: 30116

South Asian (SAS) AF: 0.00 AC: 0 AN: 75850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 0.00000654 AC: 7 AN: 1069962

Other (OTH) AF: 0.00 AC: 0 AN: 55738

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152162 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74328

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.97
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.070
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.45
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.15
Sift	Uncertain	0.015	D
Sift4G	Benign	0.10	T
Polyphen		0.80	P
Vest4		0.16
MutPred		0.72		Loss of methylation at R43 (P = 0.1481)
MVP		0.66
MPC		0.62
ClinPred		0.91	D
GERP RS		2.9
PromoterAI		0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.70
Mutation Taster		=83/17	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

dbSNP: rs1409900151; hg19: chr16-66638852;