Genetic Variant GLT8D1:c.329+139A>G (chr3-52697582-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018446.4(GLT8D1):c.329+139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 680,330 control chromosomes in the GnomAD database, including 64,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16112 hom., cov: 32)

Exomes 𝑓: 0.42 ( 48357 hom. )

Consequence

GLT8D1
NM_018446.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.00200

Publications

20 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 3-52697582-T-C is Benign according to our data. Variant chr3-52697582-T-C is described in ClinVar as [Benign]. Clinvar id is 1253649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLT8D1	NM_018446.4 link	c.329+139A>G		intron_variant	Intron 4 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.329+139A>G		intron_variant	Intron 4 of 9	1	NM_018446.4	ENSP00000266014.5		Q68CQ7-1

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69135

AN:

151838

Hom.:

16092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.454

GnomAD4 exome

AF:

0.422

AC:

222741

AN:

528374

Hom.:

48357

Cov.:

AF XY:

0.412

AC XY:

115952

AN XY:

281702

show subpopulations

African (AFR)

AF:

0.529

AC:

7944

AN:

15004

American (AMR)

AF:

0.550

AC:

16295

AN:

29612

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

7529

AN:

15822

East Asian (EAS)

AF:

0.485

AC:

16750

AN:

34554

South Asian (SAS)

AF:

0.270

AC:

14482

AN:

53730

European-Finnish (FIN)

AF:

0.407

AC:

14478

AN:

35596

Middle Eastern (MID)

AF:

0.461

AC:

976

AN:

2116

European-Non Finnish (NFE)

AF:

0.423

AC:

132127

AN:

312722

Other (OTH)

AF:

0.416

AC:

12160

AN:

29218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6511

13022

19533

26044

32555

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.455

AC:

69210

AN:

151956

Hom.:

16112

Cov.:

AF XY:

0.454

AC XY:

33743

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.522

AC:

21641

AN:

41434

American (AMR)

AF:

0.522

AC:

7967

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

1615

AN:

3466

East Asian (EAS)

AF:

0.430

AC:

2221

AN:

5170

South Asian (SAS)

AF:

0.269

AC:

1293

AN:

4810

European-Finnish (FIN)

AF:

0.398

AC:

4201

AN:

10546

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.423

AC:

28744

AN:

67954

Other (OTH)

AF:

0.459

AC:

966

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1896

3793

5689

7586

9482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.435

Hom.:

6872

Bravo

AF:

0.470

Asia WGS

AF:

0.379

AC:

1318

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 12, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.3

(source)

DANN

Benign

0.69

PhyloP100

0.0020

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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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3-52697582-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over