17-15437942-G-T

Variant names:

• chr17-15437942-G-T
• NM_001204477.2:c.290C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001204477.2(CDRT4):​c.290C>A​(p.Ser97Tyr) 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. 13/16 in silico tools predict 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: 0.188
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.088395864).

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.290C>A	p.Ser97Tyr	missense	Exon 4 of 4	NP_001191406.1	Q8N9R6
	TVP23C-CDRT4	NM_001204478.2		c.*304C>A		3_prime_UTR	Exon 7 of 7	NP_001191407.1	A0A0A6YYB9
	TVP23C-CDRT4	NR_037924.2		n.689C>A		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.290C>A	p.Ser97Tyr	missense	Exon 4 of 4	ENSP00000482523.1	Q8N9R6
	TVP23C-CDRT4	ENST00000522212.6	TSL:2	c.*304C>A		3_prime_UTR	Exon 7 of 7	ENSP00000429865.1
	CDRT4	ENST00000885788.1		c.290C>A	p.Ser97Tyr	missense	Exon 3 of 3	ENSP00000555847.1

Frequencies

GnomAD3 genomes Cov.: 32

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	Benign	0.17
PhyloP100		0.19
gMVP		0.069

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-15341259;