rs12064812

Variant names:

• chr1-219925018-T-C
• rs12064812
• NM_018713.3:c.718+2010A>G

Variant summary

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

The NM_018713.3(SLC30A10):​c.718+2010A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,026 control chromosomes in the GnomAD database, including 6,685 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 0.28 (6685 hom., cov: 31)
• Consequence: SLC30A10 NM_018713.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A10	NM_018713.3	c.718+2010A>G		intron_variant	Intron 2 of 3	ENST00000366926.4	NP_061183.2
SLC30A10	NM_001376929.1	c.529+2010A>G		intron_variant	Intron 2 of 3		NP_001363858.1
SLC30A10	NM_001416004.1	c.43+2010A>G		intron_variant	Intron 1 of 2		NP_001402933.1
SLC30A10	NM_001416005.1	c.43+2010A>G		intron_variant	Intron 2 of 3		NP_001402934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A10	ENST00000366926.4	c.718+2010A>G		intron_variant	Intron 2 of 3	1	NM_018713.3	ENSP00000355893.4
SLC30A10	ENST00000356609.2	n.*84+2010A>G		intron_variant	Intron 2 of 3	1		ENSP00000349018.2
SLC30A10	ENST00000696608.1	c.529+2010A>G		intron_variant	Intron 2 of 3			ENSP00000512752.1
SLC30A10	ENST00000484239.5	n.158+2010A>G		intron_variant	Intron 2 of 8	2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43030 AN: 151908 Hom.: 6681 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.283 AC: 43034 AN: 152026 Hom.: 6685 Cov.: 31 AF XY: 0.289 AC XY: 21450 AN XY: 74294

African (AFR) AF: 0.140 AC: 5830 AN: 41518

American (AMR) AF: 0.331 AC: 5050 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1059 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2054 AN: 5156

South Asian (SAS) AF: 0.389 AC: 1876 AN: 4818

European-Finnish (FIN) AF: 0.388 AC: 4104 AN: 10568

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22048 AN: 67920

Other (OTH) AF: 0.284 AC: 601 AN: 2114

Alfa AF: 0.311 Hom.: 2226

Bravo AF: 0.269

Asia WGS AF: 0.378 AC: 1314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.99
DANN	Benign	0.40
PhyloP100		-0.27
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: rs12064812; hg19: chr1-220098360; COSMIC: COSV63070742;