Genetic Variant SLC35D2:p.Thr230Ala (chr9-96336781-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007001.3(SLC35D2):c.688A>G(p.Thr230Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,555,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

SLC35D2
NM_007001.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

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:

ENSG00000285269 (HGNC:):

ENSG00000285269 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044172823).

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.688A>G	p.Thr230Ala	missense	Exon 9 of 12	NP_008932.2	Q76EJ3-1
SLC35D2	NM_001286990.2		c.489-12612A>G		intron	N/A	NP_001273919.1	Q76EJ3-2
SLC35D2	NR_104627.2		n.765A>G		non_coding_transcript_exon	Exon 9 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC35D2	ENST00000253270.13	TSL:1 MANE Select	c.688A>G	p.Thr230Ala	missense	Exon 9 of 12	ENSP00000253270.7	Q76EJ3-1
SLC35D2	ENST00000375259.9	TSL:1	c.489-12612A>G		intron	N/A	ENSP00000364408.4	Q76EJ3-2
ENSG00000285269	ENST00000643789.1		n.289A>G		non_coding_transcript_exon	Exon 5 of 22	ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000656

AC:

AN:

198278

AF XY:

0.0000563

show subpopulations

Gnomad AFR exome

AF:

0.000649

Gnomad AMR exome

AF:

0.0000993

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.000193

GnomAD4 exome

AF:

0.0000314

AC:

AN:

1403080

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

696726

show subpopulations

African (AFR)

AF:

0.000689

AC:

AN:

31912

American (AMR)

AF:

0.0000729

AC:

AN:

41146

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25256

East Asian (EAS)

AF:

0.00

AC:

AN:

38624

South Asian (SAS)

AF:

0.00

AC:

AN:

81348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51334

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5220

European-Non Finnish (NFE)

AF:

0.0000112

AC:

AN:

1070164

Other (OTH)

AF:

0.000121

AC:

AN:

58076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000263

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

41560

American (AMR)

AF:

0.0000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68030

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.000395

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.000685

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000503

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

0.066

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.021

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.44

M_CAP

Benign

0.015

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

1.7

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

REVEL

Benign

0.054

Sift

Benign

0.30

Sift4G

Benign

0.38

Polyphen

0.0060

Vest4

0.24

MVP

0.24

MPC

0.32

ClinPred

0.012

GERP RS

3.5

Varity_R

0.096

gMVP

0.31

Mutation Taster

=73/27

polymorphism

(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