chr17-14236001-T-C

Variant names:

• chr17-14236001-T-C
• NM_001007530.3:c.422A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001007530.3(CDRT15):​c.422A>G​(p.Glu141Gly) 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. 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: 33)
• Consequence: CDRT15 NM_001007530.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.194
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12676448).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007530.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDRT15	NM_001007530.3	MANE Select	c.422A>G	p.Glu141Gly	missense	Exon 3 of 3	NP_001007531.1	Q96T59
	CDRT15	NM_001348781.2		c.224A>G	p.Glu75Gly	missense	Exon 3 of 3	NP_001335710.1	F2Z3C1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDRT15	ENST00000420162.7	TSL:1 MANE Select	c.422A>G	p.Glu141Gly	missense	Exon 3 of 3	ENSP00000402355.3	Q96T59
	CDRT15	ENST00000431716.2	TSL:1	c.224A>G	p.Glu75Gly	missense	Exon 3 of 3	ENSP00000399575.2	F2Z3C1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	10
DANN	Benign	0.80
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.19
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.034
Sift	Benign	0.036	D
Sift4G	Benign	0.092	T
Polyphen		0.77	P
Vest4		0.073
MutPred		0.15		Gain of loop (P = 0.0051)
MVP		0.47
MPC		1.1
ClinPred		0.32	T
Varity_R		0.097
gMVP		0.026

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

Other links and lift over

hg19: chr17-14139318;