1-219906686-A-G

Variant names:

• chr1-219906686-A-G
• rs1776029
• ENST00000484239.5:n.398+11569T>C

Variant summary

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

The ENST00000484239.5(SLC30A10):​n.398+11569T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,052 control chromosomes in the GnomAD database, including 56,246 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 0.86 (56246 hom., cov: 30)
• Consequence: SLC30A10 ENST00000484239.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16
• Publications: 11 publications found

Genes affected

SLC30A10 (HGNC:25355): (solute carrier family 30 member 10) This gene is highly expressed in the liver and is inducible by manganese. Its protein product appears to be critical in maintaining manganese levels, and has higher specificity for manganese than zinc. Loss of function mutations appear to result in a pleomorphic phenotype, including dystonia and adult-onset parkinsonism. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Mar 2012]

SLC30A10 Gene-Disease associations (from GenCC):

• cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000484239.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A10	ENST00000484239.5	TSL:2	n.398+11569T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130244 AN: 151934 Hom.: 56204 Cov.: 30

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.857 AC: 130342 AN: 152052 Hom.: 56246 Cov.: 30 AF XY: 0.855 AC XY: 63520 AN XY: 74310

African (AFR) AF: 0.964 AC: 40005 AN: 41500

American (AMR) AF: 0.837 AC: 12790 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2671 AN: 3470

East Asian (EAS) AF: 0.872 AC: 4483 AN: 5142

South Asian (SAS) AF: 0.829 AC: 3989 AN: 4812

European-Finnish (FIN) AF: 0.803 AC: 8482 AN: 10566

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55282 AN: 67964

Other (OTH) AF: 0.835 AC: 1760 AN: 2108

Alfa AF: 0.843 Hom.: 6315

Bravo AF: 0.864

Asia WGS AF: 0.872 AC: 3035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.067
DANN	Benign	0.47
PhyloP100		-3.2

Splicing

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

Other links and lift over

dbSNP: rs1776029; hg19: chr1-220080028;