3-52696610-T-A

Variant names:

• chr3-52696610-T-A
• rs745397707
• NM_018446.4:c.379A>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_018446.4(GLT8D1):​c.379A>T​(p.Asn127Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,459,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N127D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: GLT8D1 NM_018446.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• 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):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19529396).
• BS2: High AC in GnomAdExome4 at 19 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLT8D1	NM_018446.4	MANE Select	c.379A>T	p.Asn127Tyr	missense	Exon 5 of 10	NP_060916.1	Q68CQ7-1
	GLT8D1	NM_001010983.3		c.379A>T	p.Asn127Tyr	missense	Exon 6 of 11	NP_001010983.1	Q68CQ7-1
	GLT8D1	NM_001278280.2		c.379A>T	p.Asn127Tyr	missense	Exon 6 of 11	NP_001265209.1	Q68CQ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLT8D1	ENST00000266014.11	TSL:1 MANE Select	c.379A>T	p.Asn127Tyr	missense	Exon 5 of 10	ENSP00000266014.5	Q68CQ7-1
	GLT8D1	ENST00000394783.7	TSL:1	c.379A>T	p.Asn127Tyr	missense	Exon 5 of 10	ENSP00000378263.3	Q68CQ7-1
	GLT8D1	ENST00000478968.6	TSL:1	c.379A>T	p.Asn127Tyr	missense	Exon 6 of 11	ENSP00000419612.2	Q68CQ7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251344 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1459240 Hom.: 0 Cov.: 29 AF XY: 0.0000151 AC XY: 11 AN XY: 726194

African (AFR) AF: 0.00 AC: 0 AN: 33424

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1109602

Other (OTH) AF: 0.0000166 AC: 1 AN: 60312

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.085	N
PhyloP100		0.089
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.14
Sift	Benign	0.035	D
Sift4G	Uncertain	0.043	D
Polyphen		0.95	P
Vest4		0.46
MVP		0.42
ClinPred		0.33	T
GERP RS		-0.89
Varity_R		0.14
gMVP		0.35
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs745397707; hg19: chr3-52730626;