NM_001271951.2:c.658-4819G>A

Variant names:

• chr18-36791898-C-T
• rs7226408
• NM_001271951.2:c.658-4819G>A

Variant summary

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

The NM_001271951.2(TPGS2):​c.658-4819G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 151,664 control chromosomes in the GnomAD database, including 3,691 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 0.20 (3691 hom., cov: 31)
• Consequence: TPGS2 NM_001271951.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627
• Publications: 13 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271951.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPGS2	NM_001271951.2		c.658-4819G>A		intron	N/A	NP_001258880.1
	TPGS2	NM_001330572.2		c.657+6551G>A		intron	N/A	NP_001317501.1
	TPGS2	NM_001271956.2		c.657+6551G>A		intron	N/A	NP_001258885.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPGS2	ENST00000590842.5	TSL:2	c.658-4819G>A		intron	N/A	ENSP00000464780.1
	TPGS2	ENST00000587129.5	TSL:4	c.657+6551G>A		intron	N/A	ENSP00000465551.1
	TPGS2	ENST00000614939.4	TSL:4	c.657+6551G>A		intron	N/A	ENSP00000478553.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30564 AN: 151548 Hom.: 3690 Cov.: 31

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.202 AC: 30616 AN: 151664 Hom.: 3691 Cov.: 31 AF XY: 0.200 AC XY: 14839 AN XY: 74116

African (AFR) AF: 0.331 AC: 13677 AN: 41290

American (AMR) AF: 0.198 AC: 3024 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 570 AN: 3470

East Asian (EAS) AF: 0.00214 AC: 11 AN: 5152

South Asian (SAS) AF: 0.104 AC: 498 AN: 4794

European-Finnish (FIN) AF: 0.165 AC: 1732 AN: 10522

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10573 AN: 67898

Other (OTH) AF: 0.184 AC: 385 AN: 2094

Alfa AF: 0.184 Hom.: 4347

Bravo AF: 0.209

Asia WGS AF: 0.0700 AC: 242 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	1.0
DANN	Benign	0.14
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7226408; hg19: chr18-34371861;