rs281860285

Variant names:

• chr1-219928118-TCGGGCCGGG-T
• rs281860285
• NM_018713.3:c.314_322delCCCGGCCCG

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PM4 PP3 PP5

The NM_018713.3(SLC30A10):​c.314_322delCCCGGCCCG​(p.Ala105_Pro107del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A10 NM_018713.3 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 7.65
• Publications: 3 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_018713.3.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 1-219928118-TCGGGCCGGG-T is Pathogenic according to our data. Variant chr1-219928118-TCGGGCCGGG-T is described in ClinVar as Pathogenic. ClinVar VariationId is 30885.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A10	NM_018713.3	c.314_322delCCCGGCCCG	p.Ala105_Pro107del	disruptive_inframe_deletion	Exon 1 of 4	ENST00000366926.4	NP_061183.2
SLC30A10	NM_001416005.1	c.-400_-392delCCCGGCCCG		5_prime_UTR_variant	Exon 1 of 4		NP_001402934.1
SLC30A10	NM_001376929.1	c.452-1022_452-1014delCCCGGCCCG		intron_variant	Intron 1 of 3		NP_001363858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A10	ENST00000366926.4	c.314_322delCCCGGCCCG	p.Ala105_Pro107del	disruptive_inframe_deletion	Exon 1 of 4	1	NM_018713.3	ENSP00000355893.4
SLC30A10	ENST00000356609.2	n.314_322delCCCGGCCCG		non_coding_transcript_exon_variant	Exon 1 of 4	1		ENSP00000349018.2
SLC30A10	ENST00000696608.1	c.452-1022_452-1014delCCCGGCCCG		intron_variant	Intron 1 of 3			ENSP00000512752.1
SLC30A10	ENST00000484239.5	n.81-1022_81-1014delCCCGGCCCG		intron_variant	Intron 1 of 8	2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Hypermanganesemia with dystonia, polycythemia, and cirrhosis Pathogenic:1 Other:1

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GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Mar 09, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6
Mutation Taster		=11/189	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs281860285; hg19: chr1-220101460;