Genetic Variant GLT8D1:p.Arg210His (chr3-52695944-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018446.4(GLT8D1):c.629G>A(p.Arg210His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,601,398 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0059 ( 28 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 205 hom. )

Consequence

GLT8D1
NM_018446.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.16

Variant links:

Genes affected

GLT8D1 (HGNC:24870): (glycosyltransferase 8 domain containing 1) This gene encodes a member of the glycosyltransferase family. The specific function of this protein has not been determined. Alternative splicing results in multiple transcript variants of this gene [provided by RefSeq, May 2013]

GLT8D1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019043982).

BP6

Variant 3-52695944-C-T is Benign according to our data. Variant chr3-52695944-C-T is described in ClinVar as [Benign]. Clinvar id is 1225352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLT8D1	NM_018446.4 link	c.629G>A	p.Arg210His	missense_variant	Exon 7 of 10	ENST00000266014.11	NP_060916.1	Q68CQ7-1A1LQI8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLT8D1	ENST00000266014.11 link	c.629G>A	p.Arg210His	missense_variant	Exon 7 of 10	1	NM_018446.4	ENSP00000266014.5		Q68CQ7-1

Frequencies

GnomAD3 genomes

AF:

0.00591

AC:

899

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.0855

Gnomad SAS

AF:

0.00682

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.0146

AC:

3657

AN:

251208

Hom.:

145

AF XY:

0.0119

AC XY:

1612

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.0522

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.0884

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.00784

GnomAD4 exome

AF:

0.00418

AC:

6056

AN:

1449114

Hom.:

205

Cov.:

AF XY:

0.00386

AC XY:

2783

AN XY:

721794

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.0460

Gnomad4 ASJ exome

AF:

0.00250

Gnomad4 EAS exome

AF:

0.0739

Gnomad4 SAS exome

AF:

0.00276

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.000275

Gnomad4 OTH exome

AF:

0.00655

GnomAD4 genome

AF:

0.00590

AC:

899

AN:

152284

Hom.:

Cov.:

AF XY:

0.00659

AC XY:

491

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.0185

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.0855

Gnomad4 SAS

AF:

0.00683

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00444

Hom.:

Bravo

AF:

0.00933

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0127

AC:

1548

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;T;T;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.80

.;.;.;T

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;L;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.14

T;T;T;T

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.25

B;B;B;B

Vest4

0.18

ClinPred

0.0074

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.76

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