Variant 1-99970577-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001271685.2(SLC35A3):c.41A>G(p.Asp14Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 1,535,706 control chromosomes in the GnomAD database, including 1,525 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 152 hom., cov: 32)

Exomes 𝑓: 0.043 ( 1373 hom. )

Consequence

SLC35A3
NM_001271685.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.485

Variant links:

Genes affected

SLC35A3 (HGNC:11023): (solute carrier family 35 member A3) This gene encodes a UDP-N-acetylglucosamine transporter found in the golgi apparatus membrane. In cattle, a missense mutation in this gene causes complex vertebral malformation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

SLC35A3 links:

ENSG00000283761 (HGNC:):

ENSG00000283761 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020925999).

BP6

Variant 1-99970577-A-G is Benign according to our data. Variant chr1-99970577-A-G is described in ClinVar as [Benign]. Clinvar id is 1185185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0432 (6569/152164) while in subpopulation AFR AF= 0.0505 (2097/41498). AF 95% confidence interval is 0.0487. There are 152 homozygotes in gnomad4. There are 3086 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 152 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A3	NM_012243.3 link	c.-19+415A>G		intron_variant	Intron 1 of 7	ENST00000533028.8	NP_036375.1	Q9Y2D2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A3	ENST00000533028.8 link	c.-19+415A>G		intron_variant	Intron 1 of 7	1	NM_012243.3	ENSP00000433849.1		Q9Y2D2-1
ENSG00000283761	ENST00000639037.1 link	c.-19+415A>G		intron_variant	Intron 1 of 16	5		ENSP00000492745.1		A0A1W2PSA9

Frequencies

GnomAD3 genomes

AF:

0.0430

AC:

6542

AN:

152046

Hom.:

147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0501

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0385

Gnomad ASJ

AF:

0.0386

Gnomad EAS

AF:

0.0407

Gnomad SAS

AF:

0.0319

Gnomad FIN

AF:

0.0212

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0433

Gnomad OTH

AF:

0.0504

GnomAD3 exomes

AF:

0.0379

AC:

5192

AN:

136918

Hom.:

118

AF XY:

0.0378

AC XY:

2812

AN XY:

74446

show subpopulations

Gnomad AFR exome

AF:

0.0535

Gnomad AMR exome

AF:

0.0212

Gnomad ASJ exome

AF:

0.0387

Gnomad EAS exome

AF:

0.0383

Gnomad SAS exome

AF:

0.0370

Gnomad FIN exome

AF:

0.0251

Gnomad NFE exome

AF:

0.0452

Gnomad OTH exome

AF:

0.0424

GnomAD4 exome

AF:

0.0428

AC:

59221

AN:

1383542

Hom.:

1373

Cov.:

AF XY:

0.0424

AC XY:

28956

AN XY:

682716

show subpopulations

Gnomad4 AFR exome

AF:

0.0486

Gnomad4 AMR exome

AF:

0.0226

Gnomad4 ASJ exome

AF:

0.0405

Gnomad4 EAS exome

AF:

0.0231

Gnomad4 SAS exome

AF:

0.0359

Gnomad4 FIN exome

AF:

0.0277

Gnomad4 NFE exome

AF:

0.0450

Gnomad4 OTH exome

AF:

0.0430

GnomAD4 genome

AF:

0.0432

AC:

6569

AN:

152164

Hom.:

152

Cov.:

AF XY:

0.0415

AC XY:

3086

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0505

Gnomad4 AMR

AF:

0.0384

Gnomad4 ASJ

AF:

0.0386

Gnomad4 EAS

AF:

0.0410

Gnomad4 SAS

AF:

0.0324

Gnomad4 FIN

AF:

0.0212

Gnomad4 NFE

AF:

0.0433

Gnomad4 OTH

AF:

0.0499

Alfa

AF:

0.0281

Hom.:

Bravo

AF:

0.0449

TwinsUK

AF:

0.0494

AC:

183

ALSPAC

AF:

0.0457

AC:

176

ExAC

AF:

0.0327

AC:

584

Asia WGS

AF:

0.0570

AC:

198

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -

SLC35A3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Autism spectrum disorder - epilepsy - arthrogryposis syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.9

DANN

Uncertain

0.99

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.080

REVEL

Benign

0.026

Sift

Benign

0.34

Sift4G

Benign

0.068

Polyphen

0.0

Vest4

0.041

ClinPred

0.011

GERP RS

0.61

gMVP

0.20

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