rs281860286

Positions:

• chr1-219927941-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018713.3(SLC30A10):​c.500T>C​(p.Phe167Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SLC30A10 NM_018713.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.649

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05278939).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC30A10	NM_018713.3	c.500T>C	p.Phe167Ser	missense_variant	1/4	ENST00000366926.4	NP_061183.2
SLC30A10	NM_001416005.1	c.-214T>C		5_prime_UTR_variant	1/4		NP_001402934.1
SLC30A10	NM_001376929.1	c.452-836T>C		intron_variant			NP_001363858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC30A10	ENST00000366926.4	c.500T>C	p.Phe167Ser	missense_variant	1/4	1	NM_018713.3	ENSP00000355893	P3
SLC30A10	ENST00000356609.2	c.500T>C	p.Phe167Ser	missense_variant, NMD_transcript_variant	1/4	1		ENSP00000349018
SLC30A10	ENST00000696608.1	c.452-836T>C		intron_variant				ENSP00000512752	A2
SLC30A10	ENST00000484239.5	n.81-836T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385904 Hom.: 0 Cov.: 33 AF XY: 0.00000146 AC XY: 1 AN XY: 683318

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.31e-7

Gnomad4 OTH exome AF: 0.00

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

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.2
DANN	Benign	0.62
DEOGEN2	Benign	0.063	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.82	L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.055
Sift	Benign	0.69	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.095
MutPred		0.35		Gain of glycosylation at F167 (P = 0.0037);
MVP		0.043
MPC		2.2
ClinPred		0.055	T
GERP RS		-1.3
Varity_R		0.050
gMVP		0.33

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

LitVar

Other links and lift over

dbSNP: rs281860286; hg19: chr1-220101283;