rs1147760

Variant names:

• chr18-36820739-G-A
• rs1147760
• NM_015476.4:c.86-1766C>T

Variant summary

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

The NM_015476.4(TPGS2):​c.86-1766C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,090 control chromosomes in the GnomAD database, including 8,073 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 0.27 (8073 hom., cov: 33)
• Consequence: TPGS2 NM_015476.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 5 publications found

Genes affected

TPGS2 (HGNC:24561): (tubulin polyglutamylase complex subunit 2) This gene encodes a protein that is a component of the neuronal polyglutamylase complex, which plays a role in post-translational addition of glutamate residues to C-terminal tubulin tails. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPGS2	NM_015476.4	c.86-1766C>T		intron_variant	Intron 1 of 6	ENST00000334295.9	NP_056291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPGS2	ENST00000334295.9	c.86-1766C>T		intron_variant	Intron 1 of 6	1	NM_015476.4	ENSP00000335144.3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40629 AN: 151974 Hom.: 8058 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.268 AC: 40689 AN: 152090 Hom.: 8073 Cov.: 33 AF XY: 0.264 AC XY: 19626 AN XY: 74360

African (AFR) AF: 0.563 AC: 23329 AN: 41452

American (AMR) AF: 0.179 AC: 2736 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1038 AN: 5174

South Asian (SAS) AF: 0.119 AC: 575 AN: 4822

European-Finnish (FIN) AF: 0.161 AC: 1705 AN: 10584

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9956 AN: 67994

Other (OTH) AF: 0.216 AC: 456 AN: 2110

Alfa AF: 0.185 Hom.: 4648

Bravo AF: 0.284

Asia WGS AF: 0.181 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.73
PhyloP100		-0.38
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: rs1147760; hg19: chr18-34400702;