17-15437813-C-T

Position:

chr17-15437813-C-T

Variant summary

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

The NM_001204477.2(CDRT4):c.419G>A(p.Arg140His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,614,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

CDRT4
NM_001204477.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.396

Variant links:

Genes affected

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

CDRT4 links:

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]

TVP23C-CDRT4 links:

CDRT4 (HGNC:):

CDRT4 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=0.11609265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDRT4	NM_001204477.2 linkuse as main transcript	c.419G>A	p.Arg140His	missense_variant	4/4	ENST00000619038.5	NP_001191406.1	Q8N9R6
TVP23C-CDRT4	NM_001204478.2 linkuse as main transcript	c.*433G>A		3_prime_UTR_variant	7/7		NP_001191407.1	Q96ET8-2A0A0A6YYB9
TVP23C-CDRT4	NR_037924.2 linkuse as main transcript	n.818G>A		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDRT4	ENST00000619038.5 linkuse as main transcript	c.419G>A	p.Arg140His	missense_variant	4/4	1	NM_001204477.2	ENSP00000482523.1	Q8N9R6
TVP23C-CDRT4	ENST00000522212 linkuse as main transcript	c.*433G>A		3_prime_UTR_variant	7/7	2		ENSP00000429865.1	A0A0A6YYB9
CDRT4	ENST00000519354.1 linkuse as main transcript	n.496G>A		non_coding_transcript_exon_variant	2/2	4
CDRT4	ENST00000520956.2 linkuse as main transcript	n.*46G>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251122

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135716

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000814

AC:

119

AN:

1461842

Hom.:

Cov.:

AF XY:

0.0000715

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000881

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000118

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 03, 2022

The c.419G>A (p.R140H) alteration is located in exon 4 (coding exon 2) of the CDRT4 gene. This alteration results from a G to A substitution at nucleotide position 419, causing the arginine (R) at amino acid position 140 to be replaced by a histidine (H). 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

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.71

M_CAP

Benign

0.0023

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

Sift4G

Uncertain

0.0060

Vest4

0.31

MVP

0.10

ClinPred

0.14

GERP RS

1.9

gMVP

0.058

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