16-66579864-G-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_144673.3(CMTM2):c.257G>T(p.Gly86Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000853 in 1,613,948 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00087 ( 2 hom. )
Consequence
CMTM2
NM_144673.3 missense
NM_144673.3 missense
Scores
4
8
6
Clinical Significance
Conservation
PhyloP100: 2.71
Genes affected
CMTM2 (HGNC:19173): (CKLF like MARVEL transmembrane domain containing 2) This gene belongs to the chemokine-like factor gene superfamily, a novel family that links the chemokine and the transmembrane 4 superfamilies of signaling molecules. The protein encoded by this gene may play an important role in testicular development. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.06745002).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CMTM2 | NM_144673.3 | c.257G>T | p.Gly86Val | missense_variant | 1/4 | ENST00000268595.3 | |
CMTM2 | NM_001199317.2 | c.257G>T | p.Gly86Val | missense_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CMTM2 | ENST00000268595.3 | c.257G>T | p.Gly86Val | missense_variant | 1/4 | 1 | NM_144673.3 | P1 | |
CMTM2 | ENST00000379486.6 | c.257G>T | p.Gly86Val | missense_variant | 1/3 | 1 | |||
CMTM2 | ENST00000569316.1 | c.91+166G>T | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000717 AC: 109AN: 152128Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000570 AC: 143AN: 250874Hom.: 0 AF XY: 0.000567 AC XY: 77AN XY: 135796
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GnomAD4 exome AF: 0.000867 AC: 1267AN: 1461704Hom.: 2 Cov.: 33 AF XY: 0.000817 AC XY: 594AN XY: 727126
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GnomAD4 genome AF: 0.000716 AC: 109AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60AN XY: 74436
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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 | Nov 27, 2023 | The c.257G>T (p.G86V) alteration is located in exon 1 (coding exon 1) of the CMTM2 gene. This alteration results from a G to T substitution at nucleotide position 257, causing the glycine (G) at amino acid position 86 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;T
Sift4G
Pathogenic
D;D
Polyphen
1.0
.;D
Vest4
MVP
MPC
0.88
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at