Genetic Variant NM_181553.4:c.499A>C (chr16-66609982-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181553.4(CMTM3):c.499A>C(p.Thr167Pro) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CMTM3
NM_181553.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.243

Publications

0 publications found

Variant links:

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]

CMTM3 links:

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]

CMTM4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038036674).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CMTM3	NM_181553.4	MANE Select	c.499A>C	p.Thr167Pro	missense	Exon 4 of 5	NP_853531.1	Q96MX0-1
CMTM3	NM_001363918.2		c.499A>C	p.Thr167Pro	missense	Exon 5 of 6	NP_001350847.1	Q96MX0-1
CMTM3	NM_001363923.2		c.499A>C	p.Thr167Pro	missense	Exon 5 of 6	NP_001350852.1	Q96MX0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CMTM3	ENST00000567572.6	TSL:1 MANE Select	c.499A>C	p.Thr167Pro	missense	Exon 4 of 5	ENSP00000455851.1	Q96MX0-1
CMTM3	ENST00000361909.8	TSL:1	c.499A>C	p.Thr167Pro	missense	Exon 5 of 6	ENSP00000354579.4	Q96MX0-1
CMTM3	ENST00000565922.1	TSL:1	c.125-3080A>C		intron	N/A	ENSP00000456426.1	Q96MX0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.024

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.51

M_CAP

Benign

0.0036

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.67

PhyloP100

0.24

PrimateAI

Benign

0.31

PROVEAN

Benign

0.50

REVEL

Benign

0.017

Sift

Benign

0.44

Sift4G

Benign

0.91

Polyphen

0.0010

Vest4

0.11

MutPred

0.23

Loss of phosphorylation at T167 (P = 0.0225)

MVP

0.14

MPC

0.42

ClinPred

0.015

GERP RS

-2.1

Varity_R

0.050

gMVP

0.37

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over