Variant 12-128888743-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_144669.3(GLT1D1):c.322A>G(p.Arg108Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000014 in 1,429,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GLT1D1
NM_144669.3 missense, splice_region

Scores

Splicing: ADA: 0.9011

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.29

Variant links:

Genes affected

GLT1D1 (HGNC:26483): (glycosyltransferase 1 domain containing 1) Predicted to enable glycosyltransferase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

GLT1D1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLT1D1	NM_144669.3 link	c.322A>G	p.Arg108Gly	missense_variant, splice_region_variant	3/8	ENST00000281703.11	NP_653270.1	Q96MS3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLT1D1	ENST00000281703.11 link	c.322A>G	p.Arg108Gly	missense_variant, splice_region_variant	3/8	2	NM_144669.3	ENSP00000281703.6		Q96MS3-2
GLT1D1	ENST00000442111.7 link	c.322A>G	p.Arg108Gly	missense_variant, splice_region_variant	3/12	5		ENSP00000394692.2		Q96MS3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1429722

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713246

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:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

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

Jan 10, 2023

The c.322A>G (p.R108G) alteration is located in exon 3 (coding exon 3) of the GLT1D1 gene. This alteration results from a A to G substitution at nucleotide position 322, causing the arginine (R) at amino acid position 108 to be replaced by a glycine (G). 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

0.29

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.091

T;.;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.83

D;D;D

MetaSVM

Uncertain

0.0026

MutationAssessor

Uncertain

2.5

M;M;.

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Uncertain

0.56

Sift

Benign

0.079

T;D;T

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.99, 0.72

.;D;P

Vest4

0.85

MutPred

0.50

.;.;Gain of catalytic residue at V100 (P = 0);

MVP

0.76

MPC

0.32

ClinPred

0.98

GERP RS

4.2

Varity_R

0.35

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.90

dbscSNV1_RF

Benign

0.63

SpliceAI score (max)

0.15

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