Genetic Variant SLC35D3:p.Thr247Thr (chr6-136924186-C-G) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001008783.3(SLC35D3):c.741C>G(p.Thr247Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00867 in 1,613,486 control chromosomes in the GnomAD database, including 1,041 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.045 ( 543 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 498 hom. )

Consequence

SLC35D3
NM_001008783.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.735

Publications

1 publications found

Variant links:

Genes affected

SLC35D3 (HGNC:15621): (solute carrier family 35 member D3) Predicted to enable antiporter activity and pyrimidine nucleotide-sugar transmembrane transporter activity. Predicted to be involved in carbohydrate transport and pyrimidine nucleotide-sugar transmembrane transport. Predicted to act upstream of or within energy homeostasis and positive regulation of protein exit from endoplasmic reticulum. Predicted to be located in early endosome and endoplasmic reticulum. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

SLC35D3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 6-136924186-C-G is Benign according to our data. Variant chr6-136924186-C-G is described in ClinVar as Benign. ClinVar VariationId is 1240540.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.735 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008783.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35D3	NM_001008783.3	MANE Select	c.741C>G	p.Thr247Thr	synonymous	Exon 2 of 2	NP_001008783.1	Q5M8T2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35D3	ENST00000331858.5	TSL:1 MANE Select	c.741C>G	p.Thr247Thr	synonymous	Exon 2 of 2	ENSP00000333591.4	Q5M8T2

Frequencies

GnomAD3 genomes

AF:

0.0451

AC:

6859

AN:

152178

Hom.:

536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0383

GnomAD2 exomes

AF:

0.0123

AC:

3082

AN:

250806

AF XY:

0.00855

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.00717

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000582

Gnomad OTH exome

AF:

0.00620

GnomAD4 exome

AF:

0.00486

AC:

7098

AN:

1461190

Hom.:

498

Cov.:

AF XY:

0.00418

AC XY:

3037

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.163

AC:

5471

AN:

33480

American (AMR)

AF:

0.00877

AC:

392

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00153

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000429

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52728

Middle Eastern (MID)

AF:

0.00971

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000394

AC:

438

AN:

1112008

Other (OTH)

AF:

0.0110

AC:

664

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

457

914

1372

1829

2286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

178

356

534

712

890

<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:

0.0453

AC:

6898

AN:

152296

Hom.:

543

Cov.:

AF XY:

0.0427

AC XY:

3181

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.157

AC:

6517

AN:

41542

American (AMR)

AF:

0.0166

AC:

254

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68038

Other (OTH)

AF:

0.0379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

298

596

895

1193

1491

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.00295

Hom.:

Bravo

AF:

0.0517

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

0.73

Mutation Taster

=98/2

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over