NM_012243.3:c.531G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_012243.3(SLC35A3):c.531G>C(p.Met177Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000699 in 1,584,292 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 1 hom. )

Consequence

SLC35A3
NM_012243.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.14

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012751281).

BP6

Variant 1-100011430-G-C is Benign according to our data. Variant chr1-100011430-G-C is described in ClinVar as Benign. ClinVar VariationId is 474762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A3	NM_012243.3 link	c.531G>C	p.Met177Ile	missense_variant	Exon 5 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.531G>C	p.Met177Ile	missense_variant	Exon 5 of 8	1	NM_012243.3	ENSP00000433849.1		Q9Y2D2-1
ENSG00000283761	ENST00000639037.1 link	c.531G>C	p.Met177Ile	missense_variant	Exon 5 of 17	5		ENSP00000492745.1		A0A1W2PSA9

Frequencies

GnomAD3 genomes

AF:

0.000835

AC:

127

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000945

AC:

231

AN:

244396

AF XY:

0.000990

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.000155

Gnomad ASJ exome

AF:

0.0129

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000752

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.000684

AC:

980

AN:

1432272

Hom.:

Cov.:

AF XY:

0.000707

AC XY:

504

AN XY:

713294

show subpopulations

African (AFR)

AF:

0.0000305

AC:

AN:

32834

American (AMR)

AF:

0.000162

AC:

AN:

43190

Ashkenazi Jewish (ASJ)

AF:

0.0119

AC:

305

AN:

25610

East Asian (EAS)

AF:

0.00

AC:

AN:

39060

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82600

European-Finnish (FIN)

AF:

0.0000950

AC:

AN:

52626

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.000553

AC:

604

AN:

1091600

Other (OTH)

AF:

0.000948

AC:

AN:

59060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

126

168

210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000835

AC:

127

AN:

152020

Hom.:

Cov.:

AF XY:

0.000768

AC XY:

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41398

American (AMR)

AF:

0.000262

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000947

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000838

AC:

AN:

67990

Other (OTH)

AF:

0.000958

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00139

Hom.:

Bravo

AF:

0.000884

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000939

AC:

114

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autism spectrum disorder - epilepsy - arthrogryposis syndrome

Benign:2

Dec 06, 2019

Natera, Inc.

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.060

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

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.096

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.0044

MetaRNN

Benign

0.013

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.44

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

PhyloP100

2.1

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.64

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

REVEL

Benign

0.10

Sift

Benign

0.82

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

Sift4G

Benign

0.98

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

Polyphen

0.0

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

Vest4

0.26, 0.25, 0.27

MutPred

0.37

Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);.;Gain of catalytic residue at M177 (P = 0.3387);.;Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);.;Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);.;Gain of catalytic residue at M177 (P = 0.3387);Gain of catalytic residue at M177 (P = 0.3387);

MVP

0.52

ClinPred

0.023

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.17

Mutation Taster

=62/37

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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