3-52697582-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018446.4(GLT8D1):​c.329+139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 680,330 control chromosomes in the GnomAD database, including 64,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16112 hom., cov: 32)
  • Exomes 𝑓: 0.42 (48357 hom.)
• Consequence: GLT8D1 NM_018446.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-52697582-T-C is Benign according to our data. Variant chr3-52697582-T-C is described in ClinVar as Benign. ClinVar VariationId is 1253649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLT8D1	NM_018446.4	MANE Select	c.329+139A>G		intron	N/A	NP_060916.1
	GLT8D1	NM_001010983.3		c.329+139A>G		intron	N/A	NP_001010983.1
	GLT8D1	NM_001278280.2		c.329+139A>G		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>G		intron	N/A	ENSP00000266014.5
	GLT8D1	ENST00000394783.7	TSL:1	c.329+139A>G		intron	N/A	ENSP00000378263.3
	GLT8D1	ENST00000478968.6	TSL:1	c.329+139A>G		intron	N/A	ENSP00000419612.2

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69135 AN: 151838 Hom.: 16092 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.454

GnomAD4 exome AF: 0.422 AC: 222741 AN: 528374 Hom.: 48357 Cov.: 6 AF XY: 0.412 AC XY: 115952 AN XY: 281702

African (AFR) AF: 0.529 AC: 7944 AN: 15004

American (AMR) AF: 0.550 AC: 16295 AN: 29612

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 7529 AN: 15822

East Asian (EAS) AF: 0.485 AC: 16750 AN: 34554

South Asian (SAS) AF: 0.270 AC: 14482 AN: 53730

European-Finnish (FIN) AF: 0.407 AC: 14478 AN: 35596

Middle Eastern (MID) AF: 0.461 AC: 976 AN: 2116

European-Non Finnish (NFE) AF: 0.423 AC: 132127 AN: 312722

Other (OTH) AF: 0.416 AC: 12160 AN: 29218

GnomAD4 genome AF: 0.455 AC: 69210 AN: 151956 Hom.: 16112 Cov.: 32 AF XY: 0.454 AC XY: 33743 AN XY: 74280

African (AFR) AF: 0.522 AC: 21641 AN: 41434

American (AMR) AF: 0.522 AC: 7967 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1615 AN: 3466

East Asian (EAS) AF: 0.430 AC: 2221 AN: 5170

South Asian (SAS) AF: 0.269 AC: 1293 AN: 4810

European-Finnish (FIN) AF: 0.398 AC: 4201 AN: 10546

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28744 AN: 67954

Other (OTH) AF: 0.459 AC: 966 AN: 2104

Alfa AF: 0.435 Hom.: 6872

Bravo AF: 0.470

Asia WGS AF: 0.379 AC: 1318 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.69
PhyloP100		0.0020
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3733041; hg19: chr3-52731598;