Genetic Variant GLT8D1:c.-36-69delA (chr3-52700564-CT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_018446.4(GLT8D1):c.-36-69delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 502,968 control chromosomes in the GnomAD database, including 197 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.036 ( 195 hom., cov: 31)

Exomes 𝑓: 0.33 ( 2 hom. )

Consequence

GLT8D1
NM_018446.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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: Benign. The variant received -10 ACMG points.

BP6

Variant 3-52700564-CT-C is Benign according to our data. Variant chr3-52700564-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1236734.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5100

AN:

141940

Hom.:

195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00793

Gnomad SAS

AF:

0.00294

Gnomad FIN

AF:

0.0244

Gnomad MID

AF:

0.0101

Gnomad NFE

AF:

0.00636

Gnomad OTH

AF:

0.0288

GnomAD4 exome

AF:

0.325

AC:

117467

AN:

361008

Hom.:

Cov.:

AF XY:

0.324

AC XY:

61676

AN XY:

190120

show subpopulations

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

African (AFR)

AF:

0.365

AC:

3914

AN:

10732

American (AMR)

AF:

0.324

AC:

5486

AN:

16920

Ashkenazi Jewish (ASJ)

AF:

0.340

AC:

3599

AN:

10594

East Asian (EAS)

AF:

0.346

AC:

9384

AN:

27110

South Asian (SAS)

AF:

0.305

AC:

8899

AN:

29216

European-Finnish (FIN)

AF:

0.316

AC:

7814

AN:

24728

Middle Eastern (MID)

AF:

0.328

AC:

487

AN:

1484

European-Non Finnish (NFE)

AF:

0.323

AC:

71052

AN:

219782

Other (OTH)

AF:

0.334

AC:

6832

AN:

20442

⚠️ 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: 0.320

Heterozygous variant carriers

7919

15838

23757

31676

39595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

682

1364

2046

2728

3410

<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:

0.0360

AC:

5112

AN:

141960

Hom.:

195

Cov.:

AF XY:

0.0362

AC XY:

2494

AN XY:

68856

show subpopulations

African (AFR)

AF:

0.104

AC:

4071

AN:

39008

American (AMR)

AF:

0.0190

AC:

269

AN:

14154

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3310

East Asian (EAS)

AF:

0.00796

AC:

AN:

4898

South Asian (SAS)

AF:

0.00296

AC:

AN:

4398

European-Finnish (FIN)

AF:

0.0244

AC:

210

AN:

8590

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.00637

AC:

411

AN:

64490

Other (OTH)

AF:

0.0287

AC:

AN:

1954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

199

398

598

797

996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(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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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