rs372158434

Variant names:

• chr17-14236589-A-G
• rs372158434
• NM_001007530.3:c.245T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001007530.3(CDRT15):​c.245T>C​(p.Ile82Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,508,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: CDRT15 NM_001007530.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.65
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009784639).

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.245T>C	p.Ile82Thr	missense	Exon 1 of 3	NP_001007531.1	Q96T59
	CDRT15	NM_001348781.2		c.64+107T>C		intron	N/A	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.245T>C	p.Ile82Thr	missense	Exon 1 of 3	ENSP00000402355.3	Q96T59
	CDRT15	ENST00000431716.2	TSL:1	c.64+107T>C		intron	N/A	ENSP00000399575.2	F2Z3C1

Frequencies

GnomAD3 genomes AF: 0.000297 AC: 45 AN: 151648 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000437

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.00252

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000255 AC: 30 AN: 117740 AF XY: 0.000330

Gnomad AFR exome AF: 0.000121

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000350

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000630

Gnomad OTH exome AF: 0.000318

GnomAD4 exome AF: 0.000141 AC: 191 AN: 1356892 Hom.: 0 Cov.: 45 AF XY: 0.000180 AC XY: 120 AN XY: 665048

African (AFR) AF: 0.000328 AC: 10 AN: 30472

American (AMR) AF: 0.0000680 AC: 2 AN: 29396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21156

East Asian (EAS) AF: 0.000438 AC: 16 AN: 36540

South Asian (SAS) AF: 0.00185 AC: 131 AN: 70636

European-Finnish (FIN) AF: 0.0000210 AC: 1 AN: 47696

Middle Eastern (MID) AF: 0.000375 AC: 2 AN: 5332

European-Non Finnish (NFE) AF: 0.0000208 AC: 22 AN: 1059678

Other (OTH) AF: 0.000125 AC: 7 AN: 55986

GnomAD4 genome AF: 0.000303 AC: 46 AN: 151766 Hom.: 0 Cov.: 29 AF XY: 0.000364 AC XY: 27 AN XY: 74172

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000459 AC: 19 AN: 41354

American (AMR) AF: 0.0000657 AC: 1 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.00252 AC: 12 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67918

Other (OTH) AF: 0.00 AC: 0 AN: 2098

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000382361), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000306 Hom.: 0

ExAC AF: 0.000139 AC: 16

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	0.11
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.17
DANN	Benign	0.44
DEOGEN2	Benign	0.030	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.00023	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.0098	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-1.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.027
Sift	Benign	0.19	T
Sift4G	Uncertain	0.050	T
Polyphen		0.0	B
Vest4		0.034
MVP		0.14
MPC		1.2
ClinPred		0.19	T
GERP RS		-0.26
PromoterAI		0.0022	Neutral
Varity_R		0.078
gMVP		0.020
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs372158434; hg19: chr17-14139906;