NM_001204477.2:c.310G>C

Variant names:

• chr17-15437922-C-G
• rs146969230
• NM_001204477.2:c.310G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001204477.2(CDRT4):​c.310G>C​(p.Ala104Pro) 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. 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. A104T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDRT4 NM_001204477.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029052228).

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.310G>C	p.Ala104Pro	missense	Exon 4 of 4	NP_001191406.1	Q8N9R6
	TVP23C-CDRT4	NM_001204478.2		c.*324G>C		3_prime_UTR	Exon 7 of 7	NP_001191407.1	A0A0A6YYB9
	TVP23C-CDRT4	NR_037924.2		n.709G>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.310G>C	p.Ala104Pro	missense	Exon 4 of 4	ENSP00000482523.1	Q8N9R6
	TVP23C-CDRT4	ENST00000522212.6	TSL:2	c.*324G>C		3_prime_UTR	Exon 7 of 7	ENSP00000429865.1
	CDRT4	ENST00000885788.1		c.310G>C	p.Ala104Pro	missense	Exon 3 of 3	ENSP00000555847.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.0010
DANN	Benign	0.63
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.6
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.0
PrimateAI	Benign	0.22	T
Sift4G	Benign	0.30	T
Vest4		0.053
MVP		0.014
ClinPred		0.064	T
GERP RS		-8.6
gMVP		0.021

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: rs146969230; hg19: chr17-15341239;