Variant 12-128875945-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_144669.3(GLT1D1):c.100G>A(p.Val34Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000751 in 1,614,052 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 2 hom. )

Consequence

GLT1D1
NM_144669.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.681

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008176446).

BP6

Variant 12-128875945-G-A is Benign according to our data. Variant chr12-128875945-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3100355.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLT1D1	NM_001366886.1 linkuse as main transcript	c.100G>A	p.Val34Ile	missense_variant	2/12	ENST00000442111.7
GLT1D1	NR_159493.1 linkuse as main transcript	n.204G>A		non_coding_transcript_exon_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLT1D1	ENST00000442111.7 linkuse as main transcript	c.100G>A	p.Val34Ile	missense_variant	2/12	5	NM_001366886.1	P1	Q96MS3-1

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000290

AC:

AN:

251390

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000484

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000766

AC:

1119

AN:

1461774

Hom.:

Cov.:

AF XY:

0.000692

AC XY:

503

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000895

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.000611

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000590

Hom.:

Bravo

AF:

0.000706

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000305

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.63

Cadd

Benign

0.0050

Dann

Benign

0.76

DEOGEN2

Benign

0.0065

T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.0082

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.76

N;N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.29

N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.59

T;T;T

Sift4G

Benign

0.86

T;T;T

Polyphen

0.0, 0.0010

.;B;B

Vest4

0.035

MVP

0.030

MPC

0.12

ClinPred

0.0025

GERP RS

-6.6

Varity_R

0.024

gMVP

0.12

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

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