rs1057519590

Variant names:

• chr1-219927948-CG-C
• rs1057519590
• NM_018713.3:c.492delC

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The ENST00000366926.4(SLC30A10):​c.492delC​(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 ENST00000366926.4 frameshift
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.463
• Publications: 2 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: Pathogenic. The variant received 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366926.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A10	NM_018713.3	MANE Select	c.492delC	p.Gly165AlafsTer27	frameshift	Exon 1 of 4	NP_061183.2
	SLC30A10	NM_001416005.1		c.-222delC		5_prime_UTR	Exon 1 of 4	NP_001402934.1
	SLC30A10	NM_001376929.1		c.452-844delC		intron	N/A	NP_001363858.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A10	ENST00000366926.4	TSL:1 MANE Select	c.492delC	p.Gly165AlafsTer27	frameshift	Exon 1 of 4	ENSP00000355893.4
	SLC30A10	ENST00000356609.2	TSL:1	n.492delC		non_coding_transcript_exon	Exon 1 of 4	ENSP00000349018.2
	SLC30A10	ENST00000696608.1		c.452-844delC		intron	N/A	ENSP00000512752.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	Hypermanganesemia with dystonia, polycythemia, and cirrhosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.46
Mutation Taster		=3/197	disease causing (ClinVar)

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: rs1057519590; hg19: chr1-220101290;