chr3-32369914-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_178868.5(CMTM8):c.469G>T(p.Ala157Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000441 in 1,608,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
CMTM8
NM_178868.5 missense
NM_178868.5 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 6.77
Genes affected
CMTM8 (HGNC:19179): (CKLF like MARVEL transmembrane domain containing 8) This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and the transmembrane 4 superfamilies. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 3. This gene acts as a tumor suppressor, and plays a role in regulating the migration of tumor cells. The encoded protein is thought to function as a a negative regulator of epidermal growth factor-induced signaling. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32261062).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CMTM8 | NM_178868.5 | c.469G>T | p.Ala157Ser | missense_variant | 4/4 | ENST00000307526.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CMTM8 | ENST00000307526.4 | c.469G>T | p.Ala157Ser | missense_variant | 4/4 | 1 | NM_178868.5 | P1 | |
CMTM8 | ENST00000458535.6 | c.295G>T | p.Ala99Ser | missense_variant | 3/3 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152054Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251202Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135780
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GnomAD4 exome AF: 0.0000467 AC: 68AN: 1456706Hom.: 0 Cov.: 29 AF XY: 0.0000470 AC XY: 34AN XY: 724096
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152054Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74274
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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 | Mar 07, 2023 | The c.469G>T (p.A157S) alteration is located in exon 4 (coding exon 4) of the CMTM8 gene. This alteration results from a G to T substitution at nucleotide position 469, causing the alanine (A) at amino acid position 157 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;T
Polyphen
0.62
.;P
Vest4
MVP
MPC
0.61
ClinPred
D
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