Variant 1-99993576-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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:

LOC124904230 (HGNC:):

LOC124904230 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=0.001616776).

BP6

Variant 1-99993576-G-A is Benign according to our data. Variant chr1-99993576-G-A is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
SLC35A3	NM_012243.3 linkuse as main transcript	c.22G>A	p.Val8Ile	missense_variant	2/8	ENST00000533028.8	NP_036375.1
LOC124904230	XR_007066249.1 linkuse as main transcript	n.279+44154C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35A3	ENST00000533028.8 linkuse as main transcript	c.22G>A	p.Val8Ile	missense_variant	2/8	1	NM_012243.3	ENSP00000433849	P1	Q9Y2D2-1

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

GnomAD3 exomes

AF:

0.00861

AC:

2164

AN:

251286

Hom.:

AF XY:

0.00662

AC XY:

899

AN XY:

135810

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 SAS exome

AF:

0.000490

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

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.00606

Gnomad4 ASJ exome

AF:

0.00218

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000413

Gnomad4 OTH exome

AF:

0.00883

GnomAD4 genome

AF:

0.0322

AC:

4897

AN:

151954

Hom.:

283

Cov.:

AF XY:

0.0313

AC XY:

2324

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.0000949

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.0204

Alfa

AF:

0.00616

Hom.:

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 20, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autism spectrum disorder - epilepsy - arthrogryposis syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Arthrogryposis multiplex congenita

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

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

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;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

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

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