Genetic Variant GLT8D1:c.-36-69dupA (chr3-52700564-C-CT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_018446.4(GLT8D1):c.-36-69dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 532,122 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.032 ( 0 hom. )

Consequence

GLT8D1
NM_018446.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 183 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLT8D1	NM_018446.4 link	c.-36-69dupA		intron_variant	Intron 1 of 9	ENST00000266014.11	NP_060916.1	Q68CQ7-1A1LQI8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLT8D1	ENST00000266014.11 link	c.-36-69dupA		intron_variant	Intron 1 of 9	1	NM_018446.4	ENSP00000266014.5		Q68CQ7-1

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

179

AN:

142362

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000744

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00240

Gnomad ASJ

AF:

0.000905

Gnomad EAS

AF:

0.00122

Gnomad SAS

AF:

0.00385

Gnomad FIN

AF:

0.00321

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000850

Gnomad OTH

AF:

0.00359

GnomAD4 exome

AF:

0.0320

AC:

12472

AN:

389732

Hom.:

Cov.:

AF XY:

0.0322

AC XY:

6605

AN XY:

204838

show subpopulations

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

African (AFR)

AF:

0.0263

AC:

303

AN:

11514

American (AMR)

AF:

0.0276

AC:

502

AN:

18166

Ashkenazi Jewish (ASJ)

AF:

0.0300

AC:

349

AN:

11652

East Asian (EAS)

AF:

0.0298

AC:

894

AN:

30048

South Asian (SAS)

AF:

0.0345

AC:

1042

AN:

30232

European-Finnish (FIN)

AF:

0.0322

AC:

855

AN:

26542

Middle Eastern (MID)

AF:

0.0404

AC:

AN:

1632

European-Non Finnish (NFE)

AF:

0.0326

AC:

7742

AN:

237592

Other (OTH)

AF:

0.0322

AC:

719

AN:

22354

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.281

Heterozygous variant carriers

1077

2154

3230

4307

5384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

164

246

328

410

<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:

0.00129

AC:

183

AN:

142390

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

102

AN XY:

69098

show subpopulations

African (AFR)

AF:

0.000845

AC:

AN:

39052

American (AMR)

AF:

0.00240

AC:

AN:

14192

Ashkenazi Jewish (ASJ)

AF:

0.000905

AC:

AN:

3314

East Asian (EAS)

AF:

0.00122

AC:

AN:

4898

South Asian (SAS)

AF:

0.00386

AC:

AN:

4400

European-Finnish (FIN)

AF:

0.00321

AC:

AN:

8728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.000850

AC:

AN:

64686

Other (OTH)

AF:

0.00357

AC:

AN:

1960

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Mutation Taster

=298/2

polymorphism

(source)

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

Publications

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3-52700564-CTTTTT-CTTTTTT

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