Genetic Variant GLT8D1:c.-36-70_-36-69delAA (chr3-52700564-CTT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_018446.4(GLT8D1):c.-36-70_-36-69delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 510,462 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 31)

Exomes 𝑓: 0.041 ( 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLT8D1	NM_018446.4 link	c.-36-70_-36-69delAA		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.-36-70_-36-69delAA		intron_variant	Intron 1 of 9	1	NM_018446.4	ENSP00000266014.5		Q68CQ7-1

Frequencies

GnomAD3 genomes

AF:

0.000443

AC:

AN:

142176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000705

Gnomad ASJ

AF:

0.000603

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00266

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000232

Gnomad OTH

AF:

0.00154

GnomAD4 exome

AF:

0.0410

AC:

15090

AN:

368258

Hom.:

AF XY:

0.0409

AC XY:

7927

AN XY:

193674

show subpopulations

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

African (AFR)

AF:

0.0451

AC:

492

AN:

10906

American (AMR)

AF:

0.0496

AC:

850

AN:

17132

Ashkenazi Jewish (ASJ)

AF:

0.0367

AC:

401

AN:

10932

East Asian (EAS)

AF:

0.0377

AC:

1065

AN:

28276

South Asian (SAS)

AF:

0.0558

AC:

1600

AN:

28672

European-Finnish (FIN)

AF:

0.0401

AC:

1007

AN:

25100

Middle Eastern (MID)

AF:

0.0339

AC:

AN:

1536

European-Non Finnish (NFE)

AF:

0.0389

AC:

8746

AN:

224628

Other (OTH)

AF:

0.0416

AC:

877

AN:

21076

⚠️ 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: 0.267

Heterozygous variant carriers

1554

3108

4663

6217

7771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

196

294

392

490

<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:

0.000450

AC:

AN:

142204

Hom.:

Cov.:

AF XY:

0.000493

AC XY:

AN XY:

68988

show subpopulations

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

African (AFR)

AF:

0.000256

AC:

AN:

39026

American (AMR)

AF:

0.000705

AC:

AN:

14184

Ashkenazi Jewish (ASJ)

AF:

0.000603

AC:

AN:

3316

East Asian (EAS)

AF:

0.00

AC:

AN:

4894

South Asian (SAS)

AF:

0.00

AC:

AN:

4402

European-Finnish (FIN)

AF:

0.00266

AC:

AN:

8634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.000232

AC:

AN:

64628

Other (OTH)

AF:

0.00204

AC:

AN:

1960

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.288

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

=292/8

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

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

3-52700564-CTTTTT-CTTT

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