rs281860285

Positions:

• chr1-219928118-TCGGGCCGGG-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PM4 PP3 PP5

The NM_018713.3(SLC30A10):​c.314_322del​(p.Ala105_Pro107del) variant causes a 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 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 7.65

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 Likely_pathogenic. Variant got 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 id is 30885.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-219928118-TCGGGCCGGG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A10	NM_018713.3	c.314_322del	p.Ala105_Pro107del	inframe_deletion	1/4	ENST00000366926.4
SLC30A10	NM_001416005.1	c.-400_-392del		5_prime_UTR_variant	1/4
SLC30A10	NM_001376929.1	c.452-1022_452-1014del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A10	ENST00000366926.4	c.314_322del	p.Ala105_Pro107del	inframe_deletion	1/4	1	NM_018713.3	P3
SLC30A10	ENST00000356609.2	c.314_322del	p.Ala105_Pro107del	inframe_deletion, NMD_transcript_variant	1/4	1
SLC30A10	ENST00000696608.1	c.452-1022_452-1014del		intron_variant				A2
SLC30A10	ENST00000484239.5	n.81-1022_81-1014del		intron_variant, non_coding_transcript_variant		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

Pathogenic, no assertion criteria provided	literature only	OMIM	Mar 09, 2012	- -
not provided, no classification provided	literature only	GeneReviews	-	- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs281860285; hg19: chr1-220101460;