NM_001204477.2:c.101C>T

Variant names:

• chr17-15438131-G-A
• rs1479027366
• NM_001204477.2:c.101C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001204477.2(CDRT4):​c.101C>T​(p.Thr34Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDRT4 NM_001204477.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30840093).

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.101C>T	p.Thr34Ile	missense	Exon 4 of 4	NP_001191406.1	Q8N9R6
	TVP23C-CDRT4	NM_001204478.2		c.*115C>T		3_prime_UTR	Exon 7 of 7	NP_001191407.1	A0A0A6YYB9
	TVP23C-CDRT4	NR_037924.2		n.500C>T		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.101C>T	p.Thr34Ile	missense	Exon 4 of 4	ENSP00000482523.1	Q8N9R6
	TVP23C-CDRT4	ENST00000522212.6	TSL:2	c.*115C>T		3_prime_UTR	Exon 7 of 7	ENSP00000429865.1
	CDRT4	ENST00000885788.1		c.101C>T	p.Thr34Ile	missense	Exon 3 of 3	ENSP00000555847.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250776 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Uncertain	0.54
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	22
DANN	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.89	T
PhyloP100		2.0
PrimateAI	Uncertain	0.54	T
Sift4G	Uncertain	0.0070	D
Vest4		0.44
MVP		0.12
ClinPred		0.90	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.21

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: rs1479027366; hg19: chr17-15341448;