Genetic Variant SLC30A10:c.*1088G>A (chr1-219914361-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018713.3(SLC30A10):c.*1088G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 152,254 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 84 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

SLC30A10
NM_018713.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.230

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: Orphanet, Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae)

SLC30A10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-219914361-C-T is Benign according to our data. Variant chr1-219914361-C-T is described in ClinVar as Benign. ClinVar VariationId is 295576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
SLC30A10	NM_018713.3	MANE Select	c.*1088G>A	3_prime_UTR	Exon 4 of 4	NP_061183.2
SLC30A10	NM_001376929.1		c.*1088G>A	3_prime_UTR	Exon 4 of 4	NP_001363858.1	A0A8Q3WLF3
SLC30A10	NM_001416004.1		c.*1088G>A	3_prime_UTR	Exon 3 of 3	NP_001402933.1	B3KR19

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC30A10	ENST00000366926.4	TSL:1 MANE Select	c.*1088G>A	3_prime_UTR	Exon 4 of 4	ENSP00000355893.4	Q6XR72-4
SLC30A10	ENST00000356609.2	TSL:1	n.*1912G>A	non_coding_transcript_exon	Exon 4 of 4	ENSP00000349018.2	Q6XR72-3
SLC30A10	ENST00000484079.1	TSL:1	n.2364G>A	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3108

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00362

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0452

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.0851

Gnomad SAS

AF:

0.0591

Gnomad FIN

AF:

0.00821

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0196

Gnomad OTH

AF:

0.0191

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0205

AC:

3117

AN:

152254

Hom.:

Cov.:

AF XY:

0.0224

AC XY:

1665

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00361

AC:

150

AN:

41554

American (AMR)

AF:

0.0455

AC:

696

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3468

East Asian (EAS)

AF:

0.0859

AC:

445

AN:

5182

South Asian (SAS)

AF:

0.0593

AC:

286

AN:

4822

European-Finnish (FIN)

AF:

0.00821

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0196

AC:

1332

AN:

68012

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

154

309

463

618

772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0218

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hypermanganesemia with dystonia, polycythemia, and cirrhosis (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.0

(source)

DANN

Benign

0.77

PhyloP100

0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over