16-66604845-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181553.4(CMTM3):c.40C>A(p.Pro14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000221 in 1,358,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

CMTM3
NM_181553.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.211

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047492802).

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.40C>A	p.Pro14Thr	missense	Exon 1 of 5	NP_853531.1	Q96MX0-1
CMTM3	NM_001363918.2		c.40C>A	p.Pro14Thr	missense	Exon 2 of 6	NP_001350847.1	Q96MX0-1
CMTM3	NM_001363923.2		c.40C>A	p.Pro14Thr	missense	Exon 2 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.40C>A	p.Pro14Thr	missense	Exon 1 of 5	ENSP00000455851.1	Q96MX0-1
CMTM3	ENST00000361909.8	TSL:1	c.40C>A	p.Pro14Thr	missense	Exon 2 of 6	ENSP00000354579.4	Q96MX0-1
CMTM3	ENST00000565922.1	TSL:1	c.40C>A	p.Pro14Thr	missense	Exon 1 of 2	ENSP00000456426.1	Q96MX0-2

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

18048

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000829

AC:

AN:

1206184

Hom.:

Cov.:

AF XY:

0.00000680

AC XY:

AN XY:

588468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23818

American (AMR)

AF:

0.000252

AC:

AN:

11886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17160

East Asian (EAS)

AF:

0.00

AC:

AN:

26836

South Asian (SAS)

AF:

0.00

AC:

AN:

51198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3812

European-Non Finnish (NFE)

AF:

0.00000302

AC:

AN:

993284

Other (OTH)

AF:

0.0000814

AC:

AN:

49116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000131

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41560

American (AMR)

AF:

0.00105

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67956

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000257

ExAC

AF:

0.0000687

AC:

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

0.073

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.0078

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.57

M_CAP

Benign

0.048

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.21

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.13

REVEL

Benign

0.039

Sift

Benign

0.24

Sift4G

Benign

0.20

Polyphen

0.030

Vest4

0.084

MutPred

0.090

Gain of phosphorylation at P14 (P = 0.0078)

MVP

0.14

MPC

0.36

ClinPred

0.098

GERP RS

-2.0

PromoterAI

-0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.031

gMVP

0.40

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over