chr3-52700564-C-CTT

Variant names:

• chr3-52700564-C-CTT
• rs78696896
• NM_018446.4:c.-36-70_-36-69dupAA

Variant summary

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

The NM_018446.4(GLT8D1):​c.-36-70_-36-69dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00031 in 535,806 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: 𝑓 0.0000070 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00042 (0 hom.)
• Consequence: GLT8D1 NM_018446.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

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

ACMG classification

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	c.-36-70_-36-69dupAA		intron_variant	Intron 1 of 9	ENST00000266014.11	NP_060916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLT8D1	ENST00000266014.11	c.-36-70_-36-69dupAA		intron_variant	Intron 1 of 9	1	NM_018446.4	ENSP00000266014.5

Frequencies

GnomAD3 genomes AF: 0.00000702 AC: 1 AN: 142410 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000155

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000419 AC: 165 AN: 393396 Hom.: 0 Cov.: 0 AF XY: 0.000445 AC XY: 92 AN XY: 206670

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

African (AFR) AF: 0.0000860 AC: 1 AN: 11628

American (AMR) AF: 0.000436 AC: 8 AN: 18334

Ashkenazi Jewish (ASJ) AF: 0.000254 AC: 3 AN: 11822

East Asian (EAS) AF: 0.000329 AC: 10 AN: 30438

South Asian (SAS) AF: 0.000561 AC: 17 AN: 30302

European-Finnish (FIN) AF: 0.000373 AC: 10 AN: 26792

Middle Eastern (MID) AF: 0.000606 AC: 1 AN: 1650

European-Non Finnish (NFE) AF: 0.000442 AC: 106 AN: 239852

Other (OTH) AF: 0.000399 AC: 9 AN: 22578

⚠️ 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.

GnomAD4 genome AF: 0.00000702 AC: 1 AN: 142410 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 69070

African (AFR) AF: 0.00 AC: 0 AN: 38978

American (AMR) AF: 0.00 AC: 0 AN: 14190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3316

East Asian (EAS) AF: 0.00 AC: 0 AN: 4916

South Asian (SAS) AF: 0.00 AC: 0 AN: 4422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.0000155 AC: 1 AN: 64716

Other (OTH) AF: 0.00 AC: 0 AN: 1952

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs78696896; hg19: chr3-52734580;