NM_001204477.2:c.419G>C

Variant names:

• chr17-15437813-C-G
• NM_001204477.2:c.419G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001204477.2(CDRT4):​c.419G>C​(p.Arg140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CDRT4 NM_001204477.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDRT4	NM_001204477.2	c.419G>C	p.Arg140Pro	missense_variant	Exon 4 of 4	ENST00000619038.5	NP_001191406.1
TVP23C-CDRT4	NM_001204478.2	c.*433G>C		3_prime_UTR_variant	Exon 7 of 7		NP_001191407.1
TVP23C-CDRT4	NR_037924.2	n.818G>C		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDRT4	ENST00000619038.5	c.419G>C	p.Arg140Pro	missense_variant	Exon 4 of 4	1	NM_001204477.2	ENSP00000482523.1
TVP23C-CDRT4	ENST00000522212	c.*433G>C		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000429865.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461842 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727228

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	18
DANN	Uncertain	0.98
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0028	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.27	T
Sift4G	Uncertain	0.0060	D
Vest4		0.63
MVP		0.15
ClinPred		0.43	T
GERP RS		1.9
gMVP		0.16

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: chr17-15341130;