Genetic Variant SLC35D2:p.Tyr52Cys (chr9-96383480-T-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_007001.3(SLC35D2):c.155A>G(p.Tyr52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000966 in 1,490,938 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00010 ( 1 hom. )

Consequence

SLC35D2
NM_007001.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.38

Publications

0 publications found

Variant links:

Genes affected

SLC35D2 (HGNC:20799): (solute carrier family 35 member D2) Nucleotide sugars, which are synthesized in the cytosol or the nucleus, are high-energy donor substrates for glycosyltransferases located in the lumen of the endoplasmic reticulum and Golgi apparatus. Translocation of nucleotide sugars from the cytosol into the lumen compartment is mediated by specific nucleotide sugar transporters, such as SLC35D2 (Suda et al., 2004 [PubMed 15082721]).[supplied by OMIM, Mar 2008]

SLC35D2 links:

SLC35D2-HSD17B3 (HGNC:):

SLC35D2-HSD17B3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2647928).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007001.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC35D2	NM_007001.3	MANE Select	c.155A>G	p.Tyr52Cys	missense	Exon 1 of 12	NP_008932.2	Q76EJ3-1
SLC35D2	NM_001286990.2		c.155A>G	p.Tyr52Cys	missense	Exon 1 of 9	NP_001273919.1	Q76EJ3-2
SLC35D2	NR_104627.2		n.232A>G		non_coding_transcript_exon	Exon 1 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC35D2	ENST00000253270.13	TSL:1 MANE Select	c.155A>G	p.Tyr52Cys	missense	Exon 1 of 12	ENSP00000253270.7	Q76EJ3-1
SLC35D2	ENST00000375259.9	TSL:1	c.155A>G	p.Tyr52Cys	missense	Exon 1 of 9	ENSP00000364408.4	Q76EJ3-2
SLC35D2	ENST00000955257.1		c.155A>G	p.Tyr52Cys	missense	Exon 1 of 13	ENSP00000625316.1

Frequencies

GnomAD3 genomes

AF:

0.0000334

AC:

AN:

149572

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000864

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000281

AC:

AN:

135018

AF XY:

0.000393

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000419

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000104

AC:

139

AN:

1341256

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

106

AN XY:

662840

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27974

American (AMR)

AF:

0.0000290

AC:

AN:

34506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23638

East Asian (EAS)

AF:

0.00

AC:

AN:

31388

South Asian (SAS)

AF:

0.00159

AC:

124

AN:

78190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45100

Middle Eastern (MID)

AF:

0.000388

AC:

AN:

5152

European-Non Finnish (NFE)

AF:

0.00000865

AC:

AN:

1040192

Other (OTH)

AF:

0.0000544

AC:

AN:

55116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0000334

AC:

AN:

149682

Hom.:

Cov.:

AF XY:

0.0000411

AC XY:

AN XY:

73056

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41092

American (AMR)

AF:

0.00

AC:

AN:

15148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

4900

South Asian (SAS)

AF:

0.000863

AC:

AN:

4634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67156

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.0000480

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.000154

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.26

MetaSVM

Uncertain

-0.026

MutationAssessor

Uncertain

2.8

PhyloP100

3.4

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-7.3

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.66

MutPred

0.52

Loss of glycosylation at T50 (P = 0.0995)

MVP

0.45

MPC

0.72

ClinPred

0.34

GERP RS

3.1

PromoterAI

-0.22

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.81

gMVP

0.52

Mutation Taster

=50/50

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over