NM_022902.5:c.1999-762A>C

Variant names:

• chr5-69127242-A-C
• rs337253
• NM_022902.5:c.1999-762A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022902.5(SLC30A5):​c.1999-762A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,984 control chromosomes in the GnomAD database, including 11,820 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 0.39 (11820 hom., cov: 31)
• Consequence: SLC30A5 NM_022902.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A5	NM_022902.5	c.1999-762A>C		intron_variant	Intron 14 of 15	ENST00000396591.8	NP_075053.2
SLC30A5	XM_005248569.4	c.1876-762A>C		intron_variant	Intron 13 of 14		XP_005248626.1
SLC30A5	XM_006714672.5	c.1999-2205A>C		intron_variant	Intron 14 of 14		XP_006714735.1
SLC30A5	XM_017009749.2	c.1876-2205A>C		intron_variant	Intron 13 of 13		XP_016865238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A5	ENST00000396591.8	c.1999-762A>C		intron_variant	Intron 14 of 15	1	NM_022902.5	ENSP00000379836.3

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58679 AN: 151866 Hom.: 11819 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.407

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.386 AC: 58681 AN: 151984 Hom.: 11820 Cov.: 31 AF XY: 0.384 AC XY: 28504 AN XY: 74266

African (AFR) AF: 0.277 AC: 11489 AN: 41440

American (AMR) AF: 0.421 AC: 6425 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1476 AN: 3468

East Asian (EAS) AF: 0.531 AC: 2752 AN: 5178

South Asian (SAS) AF: 0.425 AC: 2047 AN: 4816

European-Finnish (FIN) AF: 0.351 AC: 3698 AN: 10536

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29604 AN: 67960

Other (OTH) AF: 0.404 AC: 854 AN: 2116

Alfa AF: 0.424 Hom.: 23467

Bravo AF: 0.385

Asia WGS AF: 0.449 AC: 1562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.66
PhyloP100		0.73
Mutation Taster		=100/0	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: rs337253; hg19: chr5-68423069;