rs3733041

Variant names:

• chr3-52697582-T-A
• rs3733041
• NM_018446.4:c.329+139A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-52697582-T-A
• chr3-52697582-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018446.4(GLT8D1):​c.329+139A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLT8D1 NM_018446.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 20 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLT8D1	NM_018446.4	MANE Select	c.329+139A>T		intron	N/A	NP_060916.1
	GLT8D1	NM_001010983.3		c.329+139A>T		intron	N/A	NP_001010983.1
	GLT8D1	NM_001278280.2		c.329+139A>T		intron	N/A	NP_001265209.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLT8D1	ENST00000266014.11	TSL:1 MANE Select	c.329+139A>T		intron	N/A	ENSP00000266014.5
	GLT8D1	ENST00000394783.7	TSL:1	c.329+139A>T		intron	N/A	ENSP00000378263.3
	GLT8D1	ENST00000478968.6	TSL:1	c.329+139A>T		intron	N/A	ENSP00000419612.2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151926 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 528920 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 282010

African (AFR) AF: 0.00 AC: 0 AN: 15020

American (AMR) AF: 0.00 AC: 0 AN: 29670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15836

East Asian (EAS) AF: 0.00 AC: 0 AN: 34574

South Asian (SAS) AF: 0.00 AC: 0 AN: 53764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2120

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 313050

Other (OTH) AF: 0.00 AC: 0 AN: 29248

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151926 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74196

African (AFR) AF: 0.0000242 AC: 1 AN: 41340

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 6872

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		0.0020

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: -13

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

Other links and lift over

dbSNP: rs3733041; hg19: chr3-52731598;