chr17-20579877-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001190790.2(CDRT15L2):​c.134C>T​(p.Thr45Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,732 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: 6.9e-7 ( 0 hom. )

Consequence

CDRT15L2
NM_001190790.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0560
Variant links:
Genes affected
CDRT15L2 (HGNC:34075): (CMT1A duplicated region transcript 15 like 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12974632).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDRT15L2NM_001190790.2 linkc.134C>T p.Thr45Ile missense_variant Exon 1 of 2 ENST00000399044.1 NP_001177719.1 A8MXV6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDRT15L2ENST00000399044.1 linkc.134C>T p.Thr45Ile missense_variant Exon 1 of 2 2 NM_001190790.2 ENSP00000382000.1 A8MXV6
CDRT15L2ENST00000661883.1 linkc.134C>T p.Thr45Ile missense_variant Exon 1 of 3 ENSP00000499342.1 A0A590UJC2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000432
AC:
1
AN:
231402
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
126146
show subpopulations
Gnomad AFR exome
AF:
0.0000755
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
6.86e-7
AC:
1
AN:
1458732
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725440
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 17, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.134C>T (p.T45I) alteration is located in exon 1 (coding exon 1) of the CDRT15L2 gene. This alteration results from a C to T substitution at nucleotide position 134, causing the threonine (T) at amino acid position 45 to be replaced by an isoleucine (I). 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
0.22
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
1.6
DANN
Benign
0.62
DEOGEN2
Benign
0.028
T
Eigen
Benign
-0.85
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.0043
N
LIST_S2
Benign
0.32
T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.91
N
REVEL
Benign
0.023
Sift
Benign
0.16
T
Sift4G
Benign
0.11
T
Vest4
0.19
MutPred
0.32
Loss of phosphorylation at T45 (P = 0.0064);
MVP
0.11
MPC
0.39
ClinPred
0.020
T
GERP RS
-0.12
Varity_R
0.028
gMVP
0.021

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs1483556773; hg19: chr17-20483190; API