5-69103062-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_022902.5(SLC30A5):​c.207G>A​(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 0.00000075 in 1,333,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G69G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: SLC30A5 NM_022902.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.9477
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP7: Synonymous conserved (PhyloP=2.94 with no splicing effect.

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>A	p.Gly69Gly	splice_region synonymous	Exon 3 of 16	NP_075053.2
	SLC30A5	NM_024055.5		c.207G>A	p.Gly69Gly	splice_region synonymous	Exon 3 of 4	NP_076960.1	Q8TAD4-3
	SLC30A5	NM_001251969.2		c.84G>A	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>A	p.Gly69Gly	splice_region synonymous	Exon 3 of 16	ENSP00000379836.3	Q8TAD4-1
	SLC30A5	ENST00000380860.8	TSL:1	c.207G>A	p.Gly69Gly	splice_region synonymous	Exon 3 of 4	ENSP00000370241.4	Q8TAD4-3
	SLC30A5	ENST00000502979.1	TSL:1	c.84G>A	p.Arg28Arg	splice_region synonymous	Exon 2 of 3	ENSP00000421251.1	Q8TAD4-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 245028 AF XY: 0.00000753

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000555

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1333694 Hom.: 0 Cov.: 20 AF XY: 0.00000149 AC XY: 1 AN XY: 669788

African (AFR) AF: 0.00 AC: 0 AN: 30332

American (AMR) AF: 0.00 AC: 0 AN: 43348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25242

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38834

South Asian (SAS) AF: 0.00 AC: 0 AN: 80916

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4838

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1001274

Other (OTH) AF: 0.00 AC: 0 AN: 55780

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 139

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Benign	0.93
PhyloP100		2.9

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.95
dbscSNV1_RF	Benign	0.58
SpliceAI score (max)		0.060		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: rs28450427; hg19: chr5-68398889;