rs1057519590

chr1-219927948-CG-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_018713.3(SLC30A10):c.492del(p.Gly165AlafsTer27) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Synonymous variant affecting the same amino acid position (i.e. P164P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A10 NM_018713.3 frameshift
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.463

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A10	NM_018713.3	c.492del	p.Gly165AlafsTer27	frameshift_variant	1/4	ENST00000366926.4
SLC30A10	NM_001416005.1	c.-222del		5_prime_UTR_variant	1/4
SLC30A10	NM_001376929.1	c.452-844del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A10	ENST00000366926.4	c.492del	p.Gly165AlafsTer27	frameshift_variant	1/4	1	NM_018713.3	P3
SLC30A10	ENST00000356609.2	c.492del	p.Gly165AlafsTer27	frameshift_variant, NMD_transcript_variant	1/4	1
SLC30A10	ENST00000696608.1	c.452-844del		intron_variant				A2
SLC30A10	ENST00000484239.5	n.81-844del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Hypermanganesemia with dystonia, polycythemia, and cirrhosis Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057519590; hg19: chr1-220101290;