17-14236422-G-C

Variant names:

• chr17-14236422-G-C
• NM_001007530.3:c.271C>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.271C>G​(p.Pro91Ala) 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: 30)
• Consequence: CDRT15 NM_001007530.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.498

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=0.10424104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDRT15	NM_001007530.3	c.271C>G	p.Pro91Ala	missense_variant	Exon 2 of 3	ENST00000420162.7	NP_001007531.1
CDRT15	NM_001348781.2	c.73C>G	p.Pro25Ala	missense_variant	Exon 2 of 3		NP_001335710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDRT15	ENST00000420162.7	c.271C>G	p.Pro91Ala	missense_variant	Exon 2 of 3	1	NM_001007530.3	ENSP00000402355.3
CDRT15	ENST00000431716.2	c.73C>G	p.Pro25Ala	missense_variant	Exon 2 of 3	1		ENSP00000399575.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.271C>G (p.P91A) alteration is located in exon 2 (coding exon 2) of the CDRT15 gene. This alteration results from a C to G substitution at nucleotide position 271, causing the proline (P) at amino acid position 91 to be replaced by an alanine (A). 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	0.081
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.092
DEOGEN2	Benign	0.056	T;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Pathogenic	-4.4	D;N
REVEL	Benign	0.063
Sift	Benign	0.61	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.88	P;.
Vest4		0.18
MutPred		0.15		Loss of catalytic residue at P91 (P = 0.0135);.;
MVP		0.47
MPC		1.1
ClinPred		0.29	T
GERP RS		0.13
Varity_R		0.055
gMVP		0.012

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr17-14139739;