Genetic Variant NM_001007530.3:c.172G>A (chr17-14236662-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001007530.3(CDRT15):c.172G>A(p.Gly58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,454,998 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: 29)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CDRT15
NM_001007530.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.418

Variant links:

Genes affected

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

CDRT15 links:

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=0.09633902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDRT15	NM_001007530.3 link	c.172G>A	p.Gly58Ser	missense_variant	Exon 1 of 3	ENST00000420162.7	NP_001007531.1
CDRT15	NM_001348781.2 link	c.64+34G>A		intron_variant	Intron 1 of 2		NP_001335710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDRT15	ENST00000420162.7 link	c.172G>A	p.Gly58Ser	missense_variant	Exon 1 of 3	1	NM_001007530.3	ENSP00000402355.3		Q96T59
CDRT15	ENST00000431716.2 link	c.64+34G>A		intron_variant	Intron 1 of 2	1		ENSP00000399575.2		F2Z3C1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000493

AC:

AN:

202758

Hom.:

AF XY:

0.00000908

AC XY:

AN XY:

110166

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1454998

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723310

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.172G>A (p.G58S) alteration is located in exon 1 (coding exon 1) of the CDRT15 gene. This alteration results from a G to A substitution at nucleotide position 172, causing the glycine (G) at amino acid position 58 to be replaced by a serine (S). 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

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.53

M_CAP

Benign

0.0038

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.2

REVEL

Benign

0.047

Sift

Uncertain

0.027

Sift4G

Benign

0.20

Polyphen

0.27

Vest4

0.10

MutPred

0.35

Gain of helix (P = 0.027);

MVP

0.20

MPC

2.1

ClinPred

0.089

GERP RS

-0.24

Varity_R

0.068

gMVP

0.033

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over