rs281860289

Positions:

• chr1-219918445-GACC-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_018713.3(SLC30A10):​c.765_767delGGT​(p.Val256del) 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 not provided (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC30A10 NM_018713.3 disruptive_inframe_deletion
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 9.15

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_018713.3. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC30A10	NM_018713.3	c.765_767delGGT	p.Val256del	disruptive_inframe_deletion	3/4	ENST00000366926.4	NP_061183.2
SLC30A10	NM_001376929.1	c.576_578delGGT	p.Val193del	disruptive_inframe_deletion	3/4		NP_001363858.1
SLC30A10	NM_001416004.1	c.90_92delGGT	p.Val31del	disruptive_inframe_deletion	2/3		NP_001402933.1
SLC30A10	NM_001416005.1	c.90_92delGGT	p.Val31del	disruptive_inframe_deletion	3/4		NP_001402934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC30A10	ENST00000366926.4	c.765_767delGGT	p.Val256del	disruptive_inframe_deletion	3/4	1	NM_018713.3	ENSP00000355893.4

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

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)		0.020		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: rs281860289; hg19: chr1-220091787;