rs164578

Variant names:

• chr5-69121816-C-T
• rs164578
• NM_022902.5:c.1692C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_022902.5(SLC30A5):​c.1692C>T​(p.His564His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,611,112 control chromosomes in the GnomAD database, including 146,739 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (12496 hom., cov: 30)
  • Exomes 𝑓: 0.43 (134243 hom.)
• Consequence: SLC30A5 NM_022902.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 23 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):

• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000248664 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.633 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A5	NM_022902.5	c.1692C>T	p.His564His	synonymous_variant	Exon 13 of 16	ENST00000396591.8	NP_075053.2
SLC30A5	XM_005248569.4	c.1569C>T	p.His523His	synonymous_variant	Exon 12 of 15		XP_005248626.1
SLC30A5	XM_006714672.5	c.1692C>T	p.His564His	synonymous_variant	Exon 13 of 15		XP_006714735.1
SLC30A5	XM_017009749.2	c.1569C>T	p.His523His	synonymous_variant	Exon 12 of 14		XP_016865238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A5	ENST00000396591.8	c.1692C>T	p.His564His	synonymous_variant	Exon 13 of 16	1	NM_022902.5	ENSP00000379836.3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60884 AN: 151630 Hom.: 12494 Cov.: 30

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.416

GnomAD2 exomes AF: 0.432 AC: 107427 AN: 248570 AF XY: 0.429

Gnomad AFR exome AF: 0.331

Gnomad AMR exome AF: 0.496

Gnomad ASJ exome AF: 0.430

Gnomad EAS exome AF: 0.539

Gnomad FIN exome AF: 0.360

Gnomad NFE exome AF: 0.427

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.427 AC: 623522 AN: 1459364 Hom.: 134243 Cov.: 36 AF XY: 0.427 AC XY: 309965 AN XY: 725918

African (AFR) AF: 0.329 AC: 11022 AN: 33456

American (AMR) AF: 0.487 AC: 21618 AN: 44388

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 11136 AN: 26096

East Asian (EAS) AF: 0.511 AC: 20250 AN: 39656

South Asian (SAS) AF: 0.424 AC: 36478 AN: 86048

European-Finnish (FIN) AF: 0.359 AC: 19123 AN: 53322

Middle Eastern (MID) AF: 0.469 AC: 2702 AN: 5758

European-Non Finnish (NFE) AF: 0.428 AC: 474975 AN: 1110344

Other (OTH) AF: 0.435 AC: 26218 AN: 60296

GnomAD4 genome AF: 0.401 AC: 60894 AN: 151748 Hom.: 12496 Cov.: 30 AF XY: 0.399 AC XY: 29578 AN XY: 74150

African (AFR) AF: 0.334 AC: 13808 AN: 41364

American (AMR) AF: 0.426 AC: 6495 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1467 AN: 3468

East Asian (EAS) AF: 0.532 AC: 2726 AN: 5122

South Asian (SAS) AF: 0.419 AC: 2014 AN: 4806

European-Finnish (FIN) AF: 0.350 AC: 3687 AN: 10522

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.434 AC: 29494 AN: 67932

Other (OTH) AF: 0.413 AC: 866 AN: 2098

Alfa AF: 0.424 Hom.: 26383

Bravo AF: 0.403

Asia WGS AF: 0.445 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	5.9
DANN	Benign	0.82
PhyloP100		0.63
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs164578; hg19: chr5-68417643; COSMIC: COSV67450219; COSMIC: COSV67450219;