Variant 12-103989553-G-A 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.905C>T(p.Ser302Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,476 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GLT8D2
NM_001384711.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

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:

Genome browser will be placed here

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.905C>T	p.Ser302Leu	missense_variant	11/11	ENST00000360814.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GLT8D2	ENST00000360814.9 linkuse as main transcript	c.905C>T	p.Ser302Leu	missense_variant	11/11	1	NM_001384711.1	P1
GLT8D2	ENST00000546436.5 linkuse as main transcript	c.905C>T	p.Ser302Leu	missense_variant	10/10	5		P1
GLT8D2	ENST00000548660.5 linkuse as main transcript	c.905C>T	p.Ser302Leu	missense_variant	11/11	2		P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249482

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134990

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:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460264

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726450

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:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

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

May 16, 2022

The c.905C>T (p.S302L) alteration is located in exon 11 (coding exon 9) of the GLT8D2 gene. This alteration results from a C to T substitution at nucleotide position 905, causing the serine (S) at amino acid position 302 to be replaced by a leucine (L). 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

Uncertain

0.34

BayesDel_addAF

Benign

-0.00050

BayesDel_noAF

Benign

-0.14

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

T;T;T

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

1.0

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.53

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.94

P;P;P

Vest4

0.42

MutPred

0.60

Gain of catalytic residue at Q307 (P = 3e-04);Gain of catalytic residue at Q307 (P = 3e-04);Gain of catalytic residue at Q307 (P = 3e-04);

MVP

0.36

MPC

0.31

ClinPred

0.96

GERP RS

5.3

Varity_R

0.32

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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