Genetic Variant GLT8D1:c.330-24A>C (chr3-52696683-T-G) – 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.330-24A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.03 in 1,268,914 control chromosomes in the GnomAD database, including 1,910 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 959 hom., cov: 32)

Exomes 𝑓: 0.024 ( 951 hom. )

Consequence

GLT8D1
NM_018446.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.468

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 (BayesDel_noAF=-0.79).

BP6

Variant 3-52696683-T-G is Benign according to our data. Variant chr3-52696683-T-G is described in ClinVar as [Benign]. Clinvar id is 1294782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLT8D1	NM_018446.4 link	c.330-24A>C		intron_variant	Intron 4 of 9	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.330-24A>C		intron_variant	Intron 4 of 9	1	NM_018446.4	ENSP00000266014.5		Q68CQ7-1

Frequencies

GnomAD3 genomes

AF:

0.0725

AC:

11028

AN:

152068

Hom.:

953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.207

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0407

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0387

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0205

Gnomad OTH

AF:

0.0598

GnomAD3 exomes

AF:

0.0315

AC:

7786

AN:

246868

Hom.:

446

AF XY:

0.0287

AC XY:

3833

AN XY:

133556

show subpopulations

Gnomad AFR exome

AF:

0.215

Gnomad AMR exome

AF:

0.0196

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0349

Gnomad FIN exome

AF:

0.00681

Gnomad NFE exome

AF:

0.0195

Gnomad OTH exome

AF:

0.0270

GnomAD4 exome

AF:

0.0242

AC:

26974

AN:

1116728

Hom.:

951

Cov.:

AF XY:

0.0238

AC XY:

13596

AN XY:

570804

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.0217

Gnomad4 ASJ exome

AF:

0.0143

Gnomad4 EAS exome

AF:

0.000158

Gnomad4 SAS exome

AF:

0.0356

Gnomad4 FIN exome

AF:

0.00607

Gnomad4 NFE exome

AF:

0.0188

Gnomad4 OTH exome

AF:

0.0316

GnomAD4 genome

AF:

0.0727

AC:

11065

AN:

152186

Hom.:

959

Cov.:

AF XY:

0.0710

AC XY:

5282

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.0405

Gnomad4 ASJ

AF:

0.0136

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0390

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.0205

Gnomad4 OTH

AF:

0.0597

Alfa

AF:

0.0378

Hom.:

103

Bravo

AF:

0.0824

Asia WGS

AF:

0.0280

AC:

100

AN:

3478

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 12, 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

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.6

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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