17-15440225-C-A

Variant names:

• chr17-15440225-C-A
• rs747353508
• NM_001204477.2:c.14G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001204477.2(CDRT4):​c.14G>T​(p.Arg5Met) 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. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDRT4 NM_001204477.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840

Genes affected

CDRT4 (HGNC:14383): (CMT1A duplicated region transcript 4)

TVP23C-CDRT4 (HGNC:42961): (TVP23C-CDRT4 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring TVP23C (trans-golgi network vesicle protein 23 homolog) and CDRT4 (CMT1A duplicated region transcript 4) genes on chromosome 17. Alternative splicing results in multiple transcript variants, one of which encodes a protein that shares sequence identity with the upstream gene product, but its C-terminus is distinct due to frameshifts relative to the downstream gene. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060701698).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDRT4	NM_001204477.2	c.14G>T	p.Arg5Met	missense_variant	Exon 3 of 4	ENST00000619038.5	NP_001191406.1
TVP23C-CDRT4	NM_001204478.2	c.*28G>T		3_prime_UTR_variant	Exon 6 of 7		NP_001191407.1
TVP23C-CDRT4	NR_037924.2	n.413G>T		non_coding_transcript_exon_variant	Exon 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDRT4	ENST00000619038.5	c.14G>T	p.Arg5Met	missense_variant	Exon 3 of 4	1	NM_001204477.2	ENSP00000482523.1
TVP23C-CDRT4	ENST00000522212	c.*28G>T		3_prime_UTR_variant	Exon 6 of 7	2		ENSP00000429865.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.3
DANN	Benign	0.54
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0078	N
LIST_S2	Benign	0.37	T;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-6.0	.;D
REVEL	Benign	0.086
Sift4G	Uncertain	0.0060	D;.
Vest4		0.19
MutPred		0.15		Loss of MoRF binding (P = 0.0147);Loss of MoRF binding (P = 0.0147);
MVP		0.014
ClinPred		0.29	T
GERP RS		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.028

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

Other links and lift over

dbSNP: rs747353508; hg19: chr17-15343539;