Genetic Variant GLT8D1:c.925+4_925+7dupAGTA (chr3-52695182-C-CTACT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_018446.4(GLT8D1):c.925+4_925+7dupAGTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,589,536 control chromosomes in the GnomAD database, including 328 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 21 hom., cov: 32)

Exomes 𝑓: 0.019 ( 307 hom. )

Consequence

GLT8D1
NM_018446.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.01

Publications

0 publications found

Variant links:

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

GLT8D1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.015 (2292/152306) while in subpopulation SAS AF = 0.036 (174/4828). AF 95% confidence interval is 0.0317. There are 21 homozygotes in GnomAd4. There are 1117 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2292 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLT8D1	NM_018446.4 link	c.925+4_925+7dupAGTA		splice_region_variant, intron_variant	Intron 9 of 9	ENST00000266014.11	NP_060916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLT8D1	ENST00000266014.11 link	c.925+7_925+8insAGTA		splice_region_variant, intron_variant	Intron 9 of 9	1	NM_018446.4	ENSP00000266014.5

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2289

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00721

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0356

Gnomad FIN

AF:

0.00575

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0224

GnomAD2 exomes

AF:

0.0161

AC:

4019

AN:

249460

AF XY:

0.0175

show subpopulations

Gnomad AFR exome

AF:

0.00776

Gnomad AMR exome

AF:

0.0110

Gnomad ASJ exome

AF:

0.0134

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00671

Gnomad NFE exome

AF:

0.0187

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.0188

AC:

26962

AN:

1437230

Hom.:

307

Cov.:

AF XY:

0.0193

AC XY:

13794

AN XY:

716510

show subpopulations

African (AFR)

AF:

0.00915

AC:

302

AN:

32996

American (AMR)

AF:

0.0113

AC:

502

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.0145

AC:

375

AN:

25782

East Asian (EAS)

AF:

0.000152

AC:

AN:

39596

South Asian (SAS)

AF:

0.0350

AC:

2998

AN:

85578

European-Finnish (FIN)

AF:

0.00604

AC:

322

AN:

53320

Middle Eastern (MID)

AF:

0.0212

AC:

121

AN:

5708

European-Non Finnish (NFE)

AF:

0.0195

AC:

21283

AN:

1090286

Other (OTH)

AF:

0.0177

AC:

1053

AN:

59490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1347

2694

4042

5389

6736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

822

1644

2466

3288

4110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0150

AC:

2292

AN:

152306

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1117

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00724

AC:

301

AN:

41586

American (AMR)

AF:

0.0207

AC:

317

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.0360

AC:

174

AN:

4828

European-Finnish (FIN)

AF:

0.00575

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0196

AC:

1334

AN:

68016

Other (OTH)

AF:

0.0227

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

120

240

359

479

599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0169

Hom.:

Bravo

AF:

0.0148

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0170

EpiControl

AF:

0.0177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

3-52695182-CTACT-CTACTTACT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over