17-15518221-T-C

Variant names:

• chr17-15518221-T-C
• rs12948266
• ENST00000225576.7:c.463-14989A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145301.3(TVP23C):​c.463-14989A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 133,524 control chromosomes in the GnomAD database, including 1,128 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1128 hom., cov: 28)
• Consequence: TVP23C NM_145301.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• Publications: 4 publications found

Genes affected

TVP23C (HGNC:30453): (trans-golgi network vesicle protein 23 homolog C) Predicted to be involved in protein secretion and vesicle-mediated transport. Predicted to be integral component of membrane. Predicted to be integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145301.3. 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
	TVP23C	NM_145301.3		c.463-14989A>G		intron	N/A	NP_660344.2	Q96ET8-1
	TVP23C-CDRT4	NM_001204478.2		c.462+27564A>G		intron	N/A	NP_001191407.1	A0A0A6YYB9
	TVP23C-CDRT4	NR_037924.2		n.352+27564A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TVP23C	ENST00000225576.7	TSL:1	c.463-14989A>G		intron	N/A	ENSP00000225576.3	Q96ET8-1
	TVP23C-CDRT4	ENST00000522212.6	TSL:2	c.462+27564A>G		intron	N/A	ENSP00000429865.1
	TVP23C-CDRT4	ENST00000481756.7	TSL:4	n.*203+27564A>G		intron	N/A	ENSP00000423249.3	E5RIS5

Frequencies

GnomAD3 genomes AF: 0.128 AC: 17142 AN: 133488 Hom.: 1125 Cov.: 28

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.0887

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0879

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.128 AC: 17157 AN: 133524 Hom.: 1128 Cov.: 28 AF XY: 0.129 AC XY: 8297 AN XY: 64508

African (AFR) AF: 0.0696 AC: 2425 AN: 34854

American (AMR) AF: 0.137 AC: 1861 AN: 13542

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 527 AN: 3192

East Asian (EAS) AF: 0.0881 AC: 390 AN: 4426

South Asian (SAS) AF: 0.171 AC: 694 AN: 4070

European-Finnish (FIN) AF: 0.162 AC: 1322 AN: 8172

Middle Eastern (MID) AF: 0.214 AC: 53 AN: 248

European-Non Finnish (NFE) AF: 0.153 AC: 9537 AN: 62322

Other (OTH) AF: 0.147 AC: 274 AN: 1864

Alfa AF: 0.137 Hom.: 851

Bravo AF: 0.112

Asia WGS AF: 0.143 AC: 497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.92
DANN	Benign	0.49
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs12948266; hg19: chr17-15421535;