rs3804769

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_004733.4(SLC33A1):c.512A>G(p.Asp171Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0653 in 1,613,918 control chromosomes in the GnomAD database, including 4,454 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 586 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3868 hom. )

Consequence

SLC33A1
NM_004733.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.63

Publications

23 publications found

Variant links:

Genes affected

SLC33A1 (HGNC:95): (solute carrier family 33 member 1) The protein encoded by this gene is required for the formation of O-acetylated (Ac) gangliosides. The encoded protein is predicted to contain 6 to 10 transmembrane domains, and a leucine zipper motif in transmembrane domain III. Defects in this gene have been reported to cause spastic paraplegia autosomal dominant type 42 (SPG42) in one Chinese family, but not in similar patients of European descent. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2010]

SLC33A1 Gene-Disease associations (from GenCC):

Huppke-Brendel syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, PanelApp Australia
hereditary spastic paraplegia 42
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Illumina, PanelApp Australia, Orphanet

SLC33A1 links:

ENSG00000284952 (HGNC:):

ENSG00000284952 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=0.0015049577).

BP6

Variant 3-155853486-T-C is Benign according to our data. Variant chr3-155853486-T-C is described in ClinVar as Benign. ClinVar VariationId is 259528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004733.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC33A1	NM_004733.4	MANE Select	c.512A>G	p.Asp171Gly	missense	Exon 1 of 6	NP_004724.1	O00400
SLC33A1	NM_001190992.2		c.512A>G	p.Asp171Gly	missense	Exon 1 of 7	NP_001177921.1	O00400
SLC33A1	NM_001363883.1		c.512A>G	p.Asp171Gly	missense	Exon 1 of 4	NP_001350812.1	A0A2R8YF57

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC33A1	ENST00000643144.2	MANE Select	c.512A>G	p.Asp171Gly	missense	Exon 1 of 6	ENSP00000496241.1	O00400
SLC33A1	ENST00000359479.7	TSL:1	c.512A>G	p.Asp171Gly	missense	Exon 1 of 7	ENSP00000352456.3	O00400
ENSG00000284952	ENST00000643876.1		n.512A>G		non_coding_transcript_exon	Exon 1 of 10	ENSP00000495323.1	A0A2R8Y6H1

Frequencies

GnomAD3 genomes

AF:

0.0780

AC:

11860

AN:

152000

Hom.:

583

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.0592

Gnomad ASJ

AF:

0.0410

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.0528

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0541

Gnomad OTH

AF:

0.0809

GnomAD2 exomes

AF:

0.0829

AC:

20842

AN:

251404

AF XY:

0.0850

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.0711

Gnomad ASJ exome

AF:

0.0380

Gnomad EAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.0532

Gnomad NFE exome

AF:

0.0558

Gnomad OTH exome

AF:

0.0587

GnomAD4 exome

AF:

0.0640

AC:

93546

AN:

1461800

Hom.:

3868

Cov.:

AF XY:

0.0667

AC XY:

48515

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.113

AC:

3779

AN:

33478

American (AMR)

AF:

0.0701

AC:

3133

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0391

AC:

1022

AN:

26136

East Asian (EAS)

AF:

0.168

AC:

6684

AN:

39698

South Asian (SAS)

AF:

0.155

AC:

13366

AN:

86258

European-Finnish (FIN)

AF:

0.0543

AC:

2899

AN:

53380

Middle Eastern (MID)

AF:

0.0463

AC:

267

AN:

5768

European-Non Finnish (NFE)

AF:

0.0523

AC:

58125

AN:

1111966

Other (OTH)

AF:

0.0707

AC:

4271

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

5454

10907

16361

21814

27268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2350

4700

7050

9400

11750

<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:

0.0781

AC:

11874

AN:

152118

Hom.:

586

Cov.:

AF XY:

0.0808

AC XY:

6006

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.110

AC:

4577

AN:

41492

American (AMR)

AF:

0.0594

AC:

908

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0410

AC:

142

AN:

3466

East Asian (EAS)

AF:

0.180

AC:

930

AN:

5164

South Asian (SAS)

AF:

0.171

AC:

824

AN:

4816

European-Finnish (FIN)

AF:

0.0528

AC:

559

AN:

10588

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0541

AC:

3677

AN:

67996

Other (OTH)

AF:

0.0796

AC:

168

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

540

1080

1621

2161

2701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0619

Hom.:

1571

Bravo

AF:

0.0783

TwinsUK

AF:

0.0510

AC:

189

ALSPAC

AF:

0.0454

AC:

175

ESP6500AA

AF:

0.100

AC:

441

ESP6500EA

AF:

0.0512

AC:

440

ExAC

AF:

0.0850

AC:

10325

Asia WGS

AF:

0.151

AC:

526

AN:

3478

EpiCase

AF:

0.0525

EpiControl

AF:

0.0537

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hereditary spastic paraplegia 42 (1)

Huppke-Brendel syndrome (1)

not specified (1)

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.051

Eigen

Benign

-0.11

Eigen_PC

Benign

0.0093

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.1

PhyloP100

3.6

PrimateAI

Benign

0.47

PROVEAN

Benign

2.1

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.031

MPC

1.3

ClinPred

0.0034

GERP RS

5.4

PromoterAI

0.0039

Neutral

(source)

Varity_R

0.047

gMVP

0.41

Mutation Taster

=91/9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over