3-52699090-C-T

Variant names:

• chr3-52699090-C-T
• rs6765687
• NM_018446.4:c.116-1156G>A

Variant summary

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

The NM_018446.4(GLT8D1):​c.116-1156G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,960 control chromosomes in the GnomAD database, including 3,616 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 (3616 hom., cov: 32)
• Consequence: GLT8D1 NM_018446.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 12 publications found

Genes affected

GLT8D1 (HGNC:24870): (glycosyltransferase 8 domain containing 1) This gene encodes a member of the glycosyltransferase family. The specific function of this protein has not been determined. Alternative splicing results in multiple transcript variants of this gene [provided by RefSeq, May 2013]

GLT8D1 Gene-Disease associations (from GenCC):

• familial amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLT8D1	NM_018446.4	c.116-1156G>A		intron_variant	Intron 3 of 9	ENST00000266014.11	NP_060916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLT8D1	ENST00000266014.11	c.116-1156G>A		intron_variant	Intron 3 of 9	1	NM_018446.4	ENSP00000266014.5

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29883 AN: 151842 Hom.: 3622 Cov.: 32

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.197 AC: 29871 AN: 151960 Hom.: 3616 Cov.: 32 AF XY: 0.202 AC XY: 15017 AN XY: 74244

African (AFR) AF: 0.0545 AC: 2258 AN: 41454

American (AMR) AF: 0.162 AC: 2479 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 894 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1501 AN: 5172

South Asian (SAS) AF: 0.253 AC: 1214 AN: 4804

European-Finnish (FIN) AF: 0.345 AC: 3625 AN: 10516

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17278 AN: 67974

Other (OTH) AF: 0.187 AC: 394 AN: 2106

Alfa AF: 0.218 Hom.: 4535

Bravo AF: 0.176

Asia WGS AF: 0.212 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.59
PhyloP100		-0.51
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: rs6765687; hg19: chr3-52733106;