Variant 12-103993504-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001384711.1(GLT8D2):c.768G>C(p.Glu256Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,557,666 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 1 hom. )

Consequence

GLT8D2
NM_001384711.1 missense, splice_region

Scores

Splicing: ADA: 0.8636

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.423

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/exons	MANE	UniProt
GLT8D2	NM_001384711.1 linkuse as main transcript	c.768G>C	p.Glu256Asp	missense_variant, splice_region_variant	10/11	ENST00000360814.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GLT8D2	ENST00000360814.9 linkuse as main transcript	c.768G>C	p.Glu256Asp	missense_variant, splice_region_variant	10/11	1	NM_001384711.1	P1
GLT8D2	ENST00000546436.5 linkuse as main transcript	c.768G>C	p.Glu256Asp	missense_variant, splice_region_variant	9/10	5		P1
GLT8D2	ENST00000548660.5 linkuse as main transcript	c.768G>C	p.Glu256Asp	missense_variant, splice_region_variant	10/11	2		P1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000678

AC:

AN:

206566

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

112232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000893

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1405416

Hom.:

Cov.:

AF XY:

0.0000201

AC XY:

AN XY:

696354

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000207

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000311

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000264

ExAC

AF:

0.0000824

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.768G>C (p.E256D) alteration is located in exon 10 (coding exon 8) of the GLT8D2 gene. This alteration results from a G to C substitution at nucleotide position 768, causing the glutamic acid (E) at amino acid position 256 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

Benign

0.15

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;T

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.0060

FATHMM_MKL

Uncertain

0.93

MetaRNN

Benign

0.056

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.94

L;L;L

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.049

D;D;D

Sift4G

Benign

0.29

T;T;T

Polyphen

0.71

P;P;P

Vest4

0.42

MutPred

0.33

Gain of catalytic residue at Y260 (P = 0.0062);Gain of catalytic residue at Y260 (P = 0.0062);Gain of catalytic residue at Y260 (P = 0.0062);

MVP

0.43

MPC

0.18

ClinPred

0.13

GERP RS

4.7

Varity_R

0.20

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.86

dbscSNV1_RF

Pathogenic

0.78

SpliceAI score (max)

0.44

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.44

Position offset: 0

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