Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_018713.3(SLC30A10):c.507delG(p.Pro170LeufsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,514 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. G169G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SLC30A10
NM_018713.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1O:1

Conservation

PhyloP100: -6.07

Publications

3 publications found

Variant links:

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

SLC30A10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 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;

PP5

Variant 1-219927933-GC-G is Pathogenic according to our data. Variant chr1-219927933-GC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 30888.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018713.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC30A10	NM_018713.3	MANE Select	c.507delG	p.Pro170LeufsTer22	frameshift	Exon 1 of 4	NP_061183.2
SLC30A10	NM_001416005.1		c.-207delG		5_prime_UTR	Exon 1 of 4	NP_001402934.1
SLC30A10	NM_001376929.1		c.452-829delG		intron	N/A	NP_001363858.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC30A10	ENST00000366926.4	TSL:1 MANE Select	c.507delG	p.Pro170LeufsTer22	frameshift	Exon 1 of 4	ENSP00000355893.4
SLC30A10	ENST00000356609.2	TSL:1	n.507delG		non_coding_transcript_exon	Exon 1 of 4	ENSP00000349018.2
SLC30A10	ENST00000696608.1		c.452-829delG		intron	N/A	ENSP00000512752.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.22e-7

AC:

AN:

1385514

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

683142

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29172

American (AMR)

AF:

0.00

AC:

AN:

34636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24542

East Asian (EAS)

AF:

0.00

AC:

AN:

33974

South Asian (SAS)

AF:

0.00

AC:

AN:

78168

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

9.31e-7

AC:

AN:

1074030

Other (OTH)

AF:

0.00

AC:

AN:

57372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hypermanganesemia with dystonia, polycythemia, and cirrhosis (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-6.1

Mutation Taster

=7/193

disease causing (ClinVar)

(source)

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

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rs281860287

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over