5-69103062-G-T

Variant names:

• chr5-69103062-G-T
• rs28450427
• NM_022902.5:c.207G>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BA1

The NM_022902.5(SLC30A5):​c.207G>T​(p.Gly69Gly) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.94
• Publications: 6 publications found

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]

SLC30A5 Gene-Disease associations (from GenCC):

• cardiomyopathy

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000248664 (HGNC:):

ACMG classification

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

• PP3: Splicing predictors support a deleterious 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 VariationId is 778192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022902.5. 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
	SLC30A5	NM_022902.5	MANE Select	c.207G>T	p.Gly69Gly	splice_region synonymous	Exon 3 of 16	NP_075053.2
	SLC30A5	NM_024055.5		c.207G>T	p.Gly69Gly	splice_region synonymous	Exon 3 of 4	NP_076960.1	Q8TAD4-3
	SLC30A5	NM_001251969.2		c.84G>T	p.Arg28Arg	splice_region synonymous	Exon 2 of 3	NP_001238898.1	Q8TAD4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A5	ENST00000396591.8	TSL:1 MANE Select	c.207G>T	p.Gly69Gly	splice_region synonymous	Exon 3 of 16	ENSP00000379836.3	Q8TAD4-1
	SLC30A5	ENST00000380860.8	TSL:1	c.207G>T	p.Gly69Gly	splice_region synonymous	Exon 3 of 4	ENSP00000370241.4	Q8TAD4-3
	SLC30A5	ENST00000502979.1	TSL:1	c.84G>T	p.Arg28Arg	splice_region synonymous	Exon 2 of 3	ENSP00000421251.1	Q8TAD4-4

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

GnomAD2 exomes AF: 0.00709 AC: 1737 AN: 245028 AF XY: 0.00518

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 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

African (AFR) AF: 0.0928 AC: 2806 AN: 30232

American (AMR) AF: 0.00604 AC: 262 AN: 43348

Ashkenazi Jewish (ASJ) AF: 0.000119 AC: 3 AN: 25242

East Asian (EAS) AF: 0.00 AC: 0 AN: 38834

South Asian (SAS) AF: 0.000297 AC: 24 AN: 80916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53130

Middle Eastern (MID) AF: 0.00455 AC: 22 AN: 4836

European-Non Finnish (NFE) AF: 0.000254 AC: 254 AN: 1001264

Other (OTH) AF: 0.00649 AC: 362 AN: 55768

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

African (AFR) AF: 0.0935 AC: 3875 AN: 41464

American (AMR) AF: 0.0107 AC: 164 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000833 AC: 4 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 67990

Other (OTH) AF: 0.0238 AC: 50 AN: 2102

Alfa AF: 0.00976 Hom.: 139

Bravo AF: 0.0312

Asia WGS AF: 0.00463 AC: 16 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Benign	0.94
PhyloP100		2.9
Mutation Taster		=15/85	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.98
Splicevardb		3.0
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

Other links and lift over

dbSNP: rs28450427; hg19: chr5-68398889;