rs74102304

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012243.3(SLC35A3):c.22G>A(p.Val8Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00632 in 1,613,610 control chromosomes in the GnomAD database, including 514 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 Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 283 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 231 hom. )

Consequence

SLC35A3
NM_012243.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.914

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

autism spectrum disorder - epilepsy - arthrogryposis syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

SLC35A3 links:

ENSG00000283761 (HGNC:):

ENSG00000283761 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001616776).

BP6

Variant 1-99993576-G-A is Benign according to our data. Variant chr1-99993576-G-A is described in ClinVar as Benign. ClinVar VariationId is 474760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A3	NM_012243.3 link	c.22G>A	p.Val8Ile	missense_variant	Exon 2 of 8	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.22G>A	p.Val8Ile	missense_variant	Exon 2 of 8	1	NM_012243.3	ENSP00000433849.1		Q9Y2D2-1
ENSG00000283761	ENST00000639037.1 link	c.22G>A	p.Val8Ile	missense_variant	Exon 2 of 17	5		ENSP00000492745.1		A0A1W2PSA9

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4880

AN:

151836

Hom.:

282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.0000949

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0206

GnomAD2 exomes

AF:

0.00861

AC:

2164

AN:

251286

AF XY:

0.00662

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.00570

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000642

Gnomad OTH exome

AF:

0.00506

GnomAD4 exome

AF:

0.00363

AC:

5304

AN:

1461656

Hom.:

231

Cov.:

AF XY:

0.00322

AC XY:

2343

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.115

AC:

3862

AN:

33460

American (AMR)

AF:

0.00606

AC:

271

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00218

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39656

South Asian (SAS)

AF:

0.000522

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.0120

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000413

AC:

459

AN:

1111890

Other (OTH)

AF:

0.00883

AC:

533

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

228

456

684

912

1140

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0322

AC:

4897

AN:

151954

Hom.:

283

Cov.:

AF XY:

0.0313

AC XY:

2324

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.111

AC:

4608

AN:

41420

American (AMR)

AF:

0.0122

AC:

186

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.000577

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00125

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.0000949

AC:

AN:

10534

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000588

AC:

AN:

67972

Other (OTH)

AF:

0.0204

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

215

431

646

862

1077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0118

Hom.:

176

Bravo

AF:

0.0361

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.117

AC:

517

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.0111

AC:

1345

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00119

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 20, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autism spectrum disorder - epilepsy - arthrogryposis syndrome

Benign:1

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Arthrogryposis multiplex congenita

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.070

.;T;T;.;.;.;.;T;.;.;.;.;.;.;.;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.89

D;.;.;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0016

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.11

.;N;N;.;N;.;.;N;.;.;.;.;.;.;.;.

PhyloP100

0.91

PrimateAI

Benign

0.45

PROVEAN

Benign

0.25

.;.;N;.;.;.;.;N;.;.;.;.;.;N;.;.

REVEL

Benign

0.039

Sift

Benign

1.0

.;.;T;.;.;.;.;T;.;.;.;.;.;T;.;.

Sift4G

Benign

0.93

.;T;T;.;.;.;.;T;.;.;.;.;.;T;.;.

Polyphen

0.0

.;B;B;.;.;.;.;B;.;.;.;.;.;.;.;.

Vest4

0.040, 0.052, 0.11

ClinPred

0.0028

GERP RS

3.6

Varity_R

0.021

gMVP

0.074

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over