Genetic Variant GLT8D2:p.Gly163Asp (chr12-103996847-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001384711.1(GLT8D2):c.488G>A(p.Gly163Asp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000622 in 1,608,266 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GLT8D2
NM_001384711.1 missense, splice_region

Scores

Splicing: ADA: 0.9996

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

Variant links:

Genes affected

GLT8D2 (HGNC:24890): (glycosyltransferase 8 domain containing 2) Predicted to enable glycosyltransferase activity. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

GLT8D2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLT8D2	NM_001384711.1 link	c.488G>A	p.Gly163Asp	missense_variant, splice_region_variant	Exon 8 of 11	ENST00000360814.9	NP_001371640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLT8D2	ENST00000360814.9 link	c.488G>A	p.Gly163Asp	missense_variant, splice_region_variant	Exon 8 of 11	1	NM_001384711.1	ENSP00000354053.4	Q9H1C3
GLT8D2	ENST00000546436.5 link	c.488G>A	p.Gly163Asp	missense_variant, splice_region_variant	Exon 7 of 10	5		ENSP00000449750.1	Q9H1C3
GLT8D2	ENST00000548660.5 link	c.488G>A	p.Gly163Asp	missense_variant, splice_region_variant	Exon 8 of 11	2		ENSP00000447450.1	Q9H1C3
GLT8D2	ENST00000552572.1 link	n.-1G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247778

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133914

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1456066

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724556

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000812

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.488G>A (p.G163D) alteration is located in exon 8 (coding exon 6) of the GLT8D2 gene. This alteration results from a G to A substitution at nucleotide position 488, causing the glycine (G) at amino acid position 163 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;.;D

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.52

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-5.2

D;D;D

REVEL

Uncertain

0.40

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.49

MutPred

0.53

Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);

MVP

0.36

MPC

0.65

ClinPred

0.99

GERP RS

5.1

Varity_R

0.76

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.94

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over