5-69103062-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3 BP6_Moderate BA1

The NM_022902.5(SLC30A5):c.207G>T(p.Gly69=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00529 in 1,485,604 control chromosomes in the GnomAD database, including 325 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (178 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (147 hom.)
• Consequence: SLC30A5 NM_022902.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.9980
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.94

Genes affected

SLC30A5 (HGNC:19089): (solute carrier family 30 member 5) This gene encodes a member of the SLC30A/ZnT family of zinc transporter proteins. ZnT proteins mediate both cellular zinc efflux and zinc sequestration into membrane-bound organelles. The encoded protein plays a role in the early secretory pathway as a heterodimer with zinc transporter 6, and may also regulate zinc sequestration into secretory granules of pancreatic beta cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 19. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.
• BP6: Variant 5-69103062-G-T is Benign according to our data. Variant chr5-69103062-G-T is described in ClinVar as [Benign]. Clinvar id is 778192.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A5	NM_022902.5	c.207G>T	p.Gly69=	splice_region_variant, synonymous_variant	3/16	ENST00000396591.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A5	ENST00000396591.8	c.207G>T	p.Gly69=	splice_region_variant, synonymous_variant	3/16	1	NM_022902.5	P1

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4111 AN: 151916 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0240

GnomAD3 exomes AF: 0.00709 AC: 1737 AN: 245028 Hom.: 72 AF XY: 0.00518 AC XY: 688 AN XY: 132732

Gnomad AFR exome AF: 0.0949

Gnomad AMR exome AF: 0.00546

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000138

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000473

Gnomad OTH exome AF: 0.00353

GnomAD4 exome AF: 0.00280 AC: 3733 AN: 1333570 Hom.: 147 Cov.: 20 AF XY: 0.00242 AC XY: 1618 AN XY: 669736

Gnomad4 AFR exome AF: 0.0928

Gnomad4 AMR exome AF: 0.00604

Gnomad4 ASJ exome AF: 0.000119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000297

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000254

Gnomad4 OTH exome AF: 0.00649

GnomAD4 genome AF: 0.0271 AC: 4122 AN: 152034 Hom.: 178 Cov.: 32 AF XY: 0.0261 AC XY: 1940 AN XY: 74318

Gnomad4 AFR AF: 0.0935

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000833

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0238

Alfa AF: 0.00417 Hom.: 35

Bravo AF: 0.0312

Asia WGS AF: 0.00463 AC: 16 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 30, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Benign	22
Dann	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.98
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.35		Position offset: 31
DS_AL_spliceai		0.42		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28450427; hg19: chr5-68398889;