Genetic Variant NM_018446.4:c.-36-71_-36-69dupAAA (chr3-52700564-C-CTTT) – 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.-36-71_-36-69dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000228 in 394,012 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), 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: not found (cov: 31)

Exomes 𝑓: 0.000023 ( 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:

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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.-36-71_-36-69dupAAA		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.-36-71_-36-69dupAAA		intron_variant	Intron 1 of 9	1	NM_018446.4	ENSP00000266014.5		Q68CQ7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000228

AC:

AN:

394012

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

207016

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

11644

American (AMR)

AF:

0.00

AC:

AN:

18358

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11846

East Asian (EAS)

AF:

0.0000328

AC:

AN:

30474

South Asian (SAS)

AF:

0.0000988

AC:

AN:

30370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1652

European-Non Finnish (NFE)

AF:

0.0000208

AC:

AN:

240218

Other (OTH)

AF:

0.00

AC:

AN:

22602

⚠️ 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: 0.236

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over