Genetic Variant NM_173851.3:c.493C>T (chr8-117157765-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_173851.3(SLC30A8):c.493C>T(p.Arg165Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,614,050 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

SLC30A8
NM_173851.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.57

Publications

7 publications found

Variant links:

Genes affected

SLC30A8 (HGNC:20303): (solute carrier family 30 member 8) The protein encoded by this gene is a zinc efflux transporter involved in the accumulation of zinc in intracellular vesicles. This gene is expressed at a high level only in the pancreas, particularly in islets of Langerhans. The encoded protein colocalizes with insulin in the secretory pathway granules of the insulin-secreting INS-1 cells. Allelic variants of this gene exist that confer susceptibility to diabetes mellitus, noninsulin-dependent (NIDDM). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

SLC30A8 links:

LOC105375716 (HGNC:):

LOC105375716 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.051922023).

BP6

Variant 8-117157765-C-T is Benign according to our data. Variant chr8-117157765-C-T is described in ClinVar as Benign. ClinVar VariationId is 3037198.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173851.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC30A8	NM_173851.3	MANE Select	c.493C>T	p.Arg165Cys	missense	Exon 4 of 8	NP_776250.2	Q8IWU4-1
SLC30A8	NM_001172811.2		c.346C>T	p.Arg116Cys	missense	Exon 6 of 10	NP_001166282.1	Q8IWU4-2
SLC30A8	NM_001172813.2		c.346C>T	p.Arg116Cys	missense	Exon 7 of 11	NP_001166284.1	Q8IWU4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC30A8	ENST00000456015.7	TSL:1 MANE Select	c.493C>T	p.Arg165Cys	missense	Exon 4 of 8	ENSP00000415011.2	Q8IWU4-1
SLC30A8	ENST00000519688.5	TSL:1	c.346C>T	p.Arg116Cys	missense	Exon 5 of 9	ENSP00000431069.1	Q8IWU4-2
SLC30A8	ENST00000521243.5	TSL:1	c.346C>T	p.Arg116Cys	missense	Exon 6 of 10	ENSP00000428545.1	Q8IWU4-2

Frequencies

GnomAD3 genomes

AF:

0.00201

AC:

305

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00687

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000477

AC:

120

AN:

251456

AF XY:

0.000316

show subpopulations

Gnomad AFR exome

AF:

0.00627

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000199

AC:

291

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00606

AC:

203

AN:

33480

American (AMR)

AF:

0.000380

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000104

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000306

AC:

AN:

1111984

Other (OTH)

AF:

0.000431

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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:

0.00201

AC:

306

AN:

152188

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00687

AC:

285

AN:

41490

American (AMR)

AF:

0.000719

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68012

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000741

Hom.:

Bravo

AF:

0.00215

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000618

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SLC30A8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Pathogenic

0.25

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.82

Eigen

Pathogenic

0.73

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.052

MetaSVM

Uncertain

0.22

MutationAssessor

Pathogenic

4.2

PhyloP100

1.6

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-7.8

REVEL

Uncertain

0.61

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.70

MVP

0.84

MPC

0.36

ClinPred

0.15

GERP RS

4.9

Varity_R

0.75

gMVP

0.82

Mutation Taster

=39/61

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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