chr17-15437813-C-G

Variant names:

• chr17-15437813-C-G
• rs774381341
• NM_001204477.2:c.419G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140L) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204477.2. 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
	CDRT4	NM_001204477.2	MANE Select	c.419G>C	p.Arg140Pro	missense	Exon 4 of 4	NP_001191406.1	Q8N9R6
	TVP23C-CDRT4	NM_001204478.2		c.*433G>C		3_prime_UTR	Exon 7 of 7	NP_001191407.1	A0A0A6YYB9
	TVP23C-CDRT4	NR_037924.2		n.818G>C		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDRT4	ENST00000619038.5	TSL:1 MANE Select	c.419G>C	p.Arg140Pro	missense	Exon 4 of 4	ENSP00000482523.1	Q8N9R6
	TVP23C-CDRT4	ENST00000522212.6	TSL:2	c.*433G>C		3_prime_UTR	Exon 7 of 7	ENSP00000429865.1
	CDRT4	ENST00000885788.1		c.419G>C	p.Arg140Pro	missense	Exon 3 of 3	ENSP00000555847.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.40
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
Mutation Taster		=95/5	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: rs774381341; hg19: chr17-15341130;