Genetic Variant NM_001008783.3:c.41T>C (chr6-136922469-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001008783.3(SLC35D3):c.41T>C(p.Val14Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000623 in 1,606,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

SLC35D3
NM_001008783.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91

Publications

0 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:

ENSG00000293197 (HGNC:):

ENSG00000293197 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3441569).

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.41T>C	p.Val14Ala	missense	Exon 1 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.41T>C	p.Val14Ala	missense	Exon 1 of 2	ENSP00000333591.4	Q5M8T2
	ENSG00000293197	ENST00000769415.1		n.62+1355A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000129

AC:

AN:

231904

AF XY:

0.0000236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000293

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000626

AC:

AN:

1454056

Hom.:

Cov.:

AF XY:

0.0000622

AC XY:

AN XY:

722928

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33210

American (AMR)

AF:

0.00

AC:

AN:

44246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25806

East Asian (EAS)

AF:

0.00

AC:

AN:

39404

South Asian (SAS)

AF:

0.00

AC:

AN:

84942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000703

AC:

AN:

1109704

Other (OTH)

AF:

0.000217

AC:

AN:

60028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.0000592

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

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:

0.0000389

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.00000829

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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.094

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

3.9

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.080

REVEL

Benign

0.18

Sift

Benign

0.36

Sift4G

Pathogenic

0.0

Polyphen

0.48

Vest4

0.60

MVP

0.32

MPC

1.5

ClinPred

0.50

GERP RS

3.4

PromoterAI

0.069

Neutral

(source)

Varity_R

0.17

gMVP

0.86

Mutation Taster

=56/44

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