rs1057519589

Positions:

• chr1-219927981-G-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_018713.3(SLC30A10):​c.460C>T​(p.Gln154*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A10 NM_018713.3 stop_gained
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.0140

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 Pathogenic. Variant got 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC30A10	NM_018713.3	c.460C>T	p.Gln154*	stop_gained	1/4	ENST00000366926.4	NP_061183.2
SLC30A10	NM_001416005.1	c.-254C>T		5_prime_UTR_variant	1/4		NP_001402934.1
SLC30A10	NM_001376929.1	c.452-876C>T		intron_variant			NP_001363858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC30A10	ENST00000366926.4	c.460C>T	p.Gln154*	stop_gained	1/4	1	NM_018713.3	ENSP00000355893.4
SLC30A10	ENST00000356609.2	n.460C>T		non_coding_transcript_exon_variant	1/4	1		ENSP00000349018.2
SLC30A10	ENST00000696608.1	c.452-876C>T		intron_variant				ENSP00000512752.1
SLC30A10	ENST00000484239.5	n.81-876C>T		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	34
DANN	Uncertain	0.99
Eigen	Uncertain	0.26
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.15	N
Vest4		0.59
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1057519589; hg19: chr1-220101323;