Variant 16-66566526-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052999.4(CMTM1):c.13C>T(p.His5Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,455,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

CMTM1
NM_052999.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.28

Variant links:

Genes affected

CMTM1 (HGNC:19172): (CKLF like MARVEL transmembrane domain containing 1) 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. The protein encoded by this gene may play an important role in testicular development. Alternatively spliced transcript variants encoding different isoforms have been identified. Naturally occurring read-through transcription occurs between this locus and the neighboring locus CKLF (chemokine-like factor).[provided by RefSeq, Feb 2011]

CMTM1 links:

CKLF-CMTM1 (HGNC:39977): (CKLF-CMTM1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring CKLF (chemokine-like factor) and CMTM1 (CKLF-like MARVEL transmembrane domain containing 1) genes on chromosome 16. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

CKLF-CMTM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03063637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMTM1	NM_052999.4 link	c.13C>T	p.His5Tyr	missense_variant	1/4	ENST00000379500.7	NP_443725.3	Q8IZ96-17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTM1	ENST00000379500.7 link	c.13C>T	p.His5Tyr	missense_variant	1/4	1	NM_052999.4	ENSP00000368814.2		Q8IZ96-17
CKLF-CMTM1	ENST00000616804.5 link	c.237+8178C>T		intron_variant		2		ENSP00000479319.1		A0A087WVB3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000529

AC:

AN:

245660

Hom.:

AF XY:

0.0000828

AC XY:

AN XY:

132930

show subpopulations

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 SAS exome

AF:

0.000433

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1455596

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

723932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000268

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2023

The c.13C>T (p.H5Y) alteration is located in exon 1 (coding exon 1) of the CMTM1 gene. This alteration results from a C to T substitution at nucleotide position 13, causing the histidine (H) at amino acid position 5 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.014

DANN

Benign

0.61

DEOGEN2

Benign

0.038

.;.;.;.;T;.;T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.50

T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.031

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;N;N;N;N;.;N;.

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.9

D;D;N;D;N;D;N;N;N

REVEL

Benign

0.052

Sift

Benign

0.071

T;T;D;T;T;.;T;T;T

Sift4G

Uncertain

0.060

T;T;T;T;T;.;T;T;T

Polyphen

0.075

B;B;B;B;B;B;B;.;B

Vest4

0.14

MutPred

0.11

Gain of phosphorylation at H5 (P = 4e-04);Gain of phosphorylation at H5 (P = 4e-04);Gain of phosphorylation at H5 (P = 4e-04);Gain of phosphorylation at H5 (P = 4e-04);Gain of phosphorylation at H5 (P = 4e-04);Gain of phosphorylation at H5 (P = 4e-04);Gain of phosphorylation at H5 (P = 4e-04);Gain of phosphorylation at H5 (P = 4e-04);Gain of phosphorylation at H5 (P = 4e-04);

MVP

0.20

MPC

0.35

ClinPred

0.039

GERP RS

-3.8

Varity_R

0.027

gMVP

0.047

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over