Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F167V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SLC30A10
NM_018713.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.649

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05278939).

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.500T>C	p.Phe167Ser	missense	Exon 1 of 4	NP_061183.2
SLC30A10	NM_001416005.1		c.-214T>C		5_prime_UTR	Exon 1 of 4	NP_001402934.1
SLC30A10	NM_001376929.1		c.452-836T>C		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.500T>C	p.Phe167Ser	missense	Exon 1 of 4	ENSP00000355893.4
SLC30A10	ENST00000356609.2	TSL:1	n.500T>C		non_coding_transcript_exon	Exon 1 of 4	ENSP00000349018.2
SLC30A10	ENST00000696608.1		c.452-836T>C		intron	N/A	ENSP00000512752.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.22e-7

AC:

AN:

1385904

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

683318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29264

American (AMR)

AF:

0.00

AC:

AN:

34712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24568

East Asian (EAS)

AF:

0.00

AC:

AN:

33980

South Asian (SAS)

AF:

0.00

AC:

AN:

78190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

9.31e-7

AC:

AN:

1074256

Other (OTH)

AF:

0.00

AC:

AN:

57388

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:not provided

Revision:no classification provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hypermanganesemia with dystonia, polycythemia, and cirrhosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.2

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.063

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.24

M_CAP

Benign

0.011

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.82

PhyloP100

0.65

PrimateAI

Uncertain

0.78

PROVEAN

Benign

0.61

REVEL

Benign

0.055

Sift

Benign

0.69

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.095

MutPred

0.35

Gain of glycosylation at F167 (P = 0.0037)

MVP

0.043

MPC

2.2

ClinPred

0.055

GERP RS

-1.3

Varity_R

0.050

gMVP

0.33

Mutation Taster

=32/68

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs281860286

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