Genetic Variant SLC35A3:c.465+1744C>T (chr1-100008900-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012243.3(SLC35A3):c.465+1744C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 152,280 control chromosomes in the GnomAD database, including 346 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.059 ( 346 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

SLC35A3
NM_012243.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.689

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012243.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC35A3	NM_012243.3	MANE Select	c.465+1744C>T	intron	N/A	NP_036375.1
SLC35A3	NM_001271685.2		c.591+1744C>T	intron	N/A	NP_001258614.1
SLC35A3	NM_001438725.1		c.465+1744C>T	intron	N/A	NP_001425654.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC35A3	ENST00000533028.8	TSL:1 MANE Select	c.465+1744C>T	intron	N/A	ENSP00000433849.1
ENSG00000283761	ENST00000639037.1	TSL:5	c.465+1744C>T	intron	N/A	ENSP00000492745.1
SLC35A3	ENST00000638336.1	TSL:1	c.465+1744C>T	intron	N/A	ENSP00000491145.1

Frequencies

GnomAD3 genomes

AF:

0.0589

AC:

8959

AN:

152160

Hom.:

347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0359

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.0507

Gnomad FIN

AF:

0.0403

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0459

Gnomad OTH

AF:

0.0511

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0588

AC:

8959

AN:

152278

Hom.:

346

Cov.:

AF XY:

0.0582

AC XY:

4337

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.104

AC:

4336

AN:

41548

American (AMR)

AF:

0.0358

AC:

547

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

3468

East Asian (EAS)

AF:

0.0154

AC:

AN:

5192

South Asian (SAS)

AF:

0.0501

AC:

242

AN:

4828

European-Finnish (FIN)

AF:

0.0403

AC:

427

AN:

10608

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0459

AC:

3123

AN:

68018

Other (OTH)

AF:

0.0497

AC:

105

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

439

878

1317

1756

2195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0502

Hom.:

131

Bravo

AF:

0.0580

Asia WGS

AF:

0.0350

AC:

120

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.2

(source)

DANN

Benign

0.71

PhyloP100

-0.69

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over