Menu
GeneBe

8-117146954-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_173851.3(SLC30A8):c.72T>C(p.Ser24=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000568 in 1,613,828 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 4 hom. )

Consequence

SLC30A8
NM_173851.3 splice_region, synonymous

Scores

2
Splicing: ADA: 0.00003876
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.733
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-117146954-T-C is Benign according to our data. Variant chr8-117146954-T-C is described in ClinVar as [Benign]. Clinvar id is 791294.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.733 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC30A8NM_173851.3 linkuse as main transcriptc.72T>C p.Ser24= splice_region_variant, synonymous_variant 2/8 ENST00000456015.7
LOC105375716XR_007061067.1 linkuse as main transcriptn.819+25661A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC30A8ENST00000456015.7 linkuse as main transcriptc.72T>C p.Ser24= splice_region_variant, synonymous_variant 2/81 NM_173851.3 P1Q8IWU4-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00302
AC:
459
AN:
152104
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0103
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00138
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.000808
AC:
203
AN:
251084
Hom.:
2
AF XY:
0.000553
AC XY:
75
AN XY:
135740
show subpopulations
Gnomad AFR exome
AF:
0.0108
Gnomad AMR exome
AF:
0.000667
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000313
AC:
457
AN:
1461608
Hom.:
4
Cov.:
31
AF XY:
0.000281
AC XY:
204
AN XY:
727102
show subpopulations
Gnomad4 AFR exome
AF:
0.0107
Gnomad4 AMR exome
AF:
0.000627
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.000894
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00302
AC:
460
AN:
152220
Hom.:
6
Cov.:
32
AF XY:
0.00300
AC XY:
223
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0103
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.000523
Hom.:
2
Bravo
AF:
0.00341
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
Cadd
Benign
3.8
Dann
Benign
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000039
dbscSNV1_RF
Benign
0.040
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144023942; hg19: chr8-118159193; API