rs12948266

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-15518221-T-A
• chr17-15518221-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145301.3(TVP23C):​c.463-14989A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0000075 (0 hom., cov: 28)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

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>T		intron	N/A	NP_660344.2	Q96ET8-1
	TVP23C-CDRT4	NM_001204478.2		c.462+27564A>T		intron	N/A	NP_001191407.1	A0A0A6YYB9
	TVP23C-CDRT4	NR_037924.2		n.352+27564A>T		intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.00000749 AC: 1 AN: 133556 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000225

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000749 AC: 1 AN: 133592 Hom.: 0 Cov.: 28 AF XY: 0.0000155 AC XY: 1 AN XY: 64556

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 34860

American (AMR) AF: 0.00 AC: 0 AN: 13556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3192

East Asian (EAS) AF: 0.000226 AC: 1 AN: 4426

South Asian (SAS) AF: 0.00 AC: 0 AN: 4072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62356

Other (OTH) AF: 0.00 AC: 0 AN: 1866

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 851

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.64
DANN	Benign	0.30
PhyloP100		-2.9

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;