chr17-14236791-T-C

Variant names:

• chr17-14236791-T-C
• NM_001007530.3:c.43A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001007530.3(CDRT15):​c.43A>G​(p.Arg15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDRT15 NM_001007530.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.926

Genes affected

CDRT15 (HGNC:14395): (CMT1A duplicated region transcript 15)

ACMG classification

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=0.17796877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDRT15	NM_001007530.3	c.43A>G	p.Arg15Gly	missense_variant	Exon 1 of 3	ENST00000420162.7	NP_001007531.1
CDRT15	NM_001348781.2	c.-32A>G		5_prime_UTR_variant	Exon 1 of 3		NP_001335710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDRT15	ENST00000420162.7	c.43A>G	p.Arg15Gly	missense_variant	Exon 1 of 3	1	NM_001007530.3	ENSP00000402355.3
CDRT15	ENST00000431716.2	c.-32A>G		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000399575.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 39

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.43A>G (p.R15G) alteration is located in exon 1 (coding exon 1) of the CDRT15 gene. This alteration results from a A to G substitution at nucleotide position 43, causing the arginine (R) at amino acid position 15 to be replaced by a glycine (G). 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	Uncertain	0.48
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.088
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.014	D
Polyphen		0.94	P
Vest4		0.22
MutPred		0.24		Loss of stability (P = 0.0386);
MVP		0.65
MPC		2.3
ClinPred		0.44	T
GERP RS		0.68
Varity_R		0.15
gMVP		0.029

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-14140108;