Genetic Variant NM_018446.4:c.329+182_329+184delGAG (chr3-52697536-TCTC-T) – 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.329+182_329+184delGAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 591,344 control chromosomes in the GnomAD database, including 374 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.033 ( 273 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 101 hom. )

Consequence

GLT8D1
NM_018446.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.624

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):

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 3-52697536-TCTC-T is Benign according to our data. Variant chr3-52697536-TCTC-T is described in ClinVar as Benign. ClinVar VariationId is 1278330.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018446.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLT8D1	NM_018446.4	MANE Select	c.329+182_329+184delGAG	intron	N/A	NP_060916.1	Q68CQ7-1
GLT8D1	NM_001010983.3		c.329+182_329+184delGAG	intron	N/A	NP_001010983.1	Q68CQ7-1
GLT8D1	NM_001278280.2		c.329+182_329+184delGAG	intron	N/A	NP_001265209.1	Q68CQ7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLT8D1	ENST00000266014.11	TSL:1 MANE Select	c.329+182_329+184delGAG	intron	N/A	ENSP00000266014.5	Q68CQ7-1
GLT8D1	ENST00000394783.7	TSL:1	c.329+182_329+184delGAG	intron	N/A	ENSP00000378263.3	Q68CQ7-1
GLT8D1	ENST00000478968.6	TSL:1	c.329+182_329+184delGAG	intron	N/A	ENSP00000419612.2	Q68CQ7-1

Frequencies

GnomAD3 genomes

AF:

0.0331

AC:

5042

AN:

152134

Hom.:

272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.0282

GnomAD4 exome

AF:

0.00471

AC:

2067

AN:

439092

Hom.:

101

AF XY:

0.00402

AC XY:

929

AN XY:

231224

show subpopulations

African (AFR)

AF:

0.111

AC:

1372

AN:

12368

American (AMR)

AF:

0.0104

AC:

204

AN:

19614

Ashkenazi Jewish (ASJ)

AF:

0.00103

AC:

AN:

13578

East Asian (EAS)

AF:

0.000164

AC:

AN:

30490

South Asian (SAS)

AF:

0.000451

AC:

AN:

44312

European-Finnish (FIN)

AF:

0.0000697

AC:

AN:

28676

Middle Eastern (MID)

AF:

0.00620

AC:

AN:

1934

European-Non Finnish (NFE)

AF:

0.000636

AC:

167

AN:

262750

Other (OTH)

AF:

0.0107

AC:

271

AN:

25370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

174

260

347

434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.0332

AC:

5049

AN:

152252

Hom.:

273

Cov.:

AF XY:

0.0318

AC XY:

2364

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.113

AC:

4704

AN:

41526

American (AMR)

AF:

0.0146

AC:

223

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000765

AC:

AN:

68018

Other (OTH)

AF:

0.0279

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

228

457

685

914

1142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0251

Hom.:

Bravo

AF:

0.0380

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.62

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over