Genetic Variant SLC30A10:c.*744G>T (chr1-219914705-C-A) – 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.*744G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,250 control chromosomes in the GnomAD database, including 55,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55384 hom., cov: 32)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

SLC30A10
NM_018713.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0350

Publications

18 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=-0.94).

BP6

Variant 1-219914705-C-A is Benign according to our data. Variant chr1-219914705-C-A is described in ClinVar as Benign. ClinVar VariationId is 295578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 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.*744G>T	3_prime_UTR	Exon 4 of 4	NP_061183.2
SLC30A10	NM_001376929.1		c.*744G>T	3_prime_UTR	Exon 4 of 4	NP_001363858.1	A0A8Q3WLF3
SLC30A10	NM_001416004.1		c.*744G>T	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.*744G>T	3_prime_UTR	Exon 4 of 4	ENSP00000355893.4	Q6XR72-4
SLC30A10	ENST00000356609.2	TSL:1	n.*1568G>T	non_coding_transcript_exon	Exon 4 of 4	ENSP00000349018.2	Q6XR72-3
SLC30A10	ENST00000484079.1	TSL:1	n.2020G>T	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.850

AC:

129280

AN:

152130

Hom.:

55341

Cov.:

show subpopulations

Gnomad AFR

AF:

0.962

Gnomad AMI

AF:

0.673

Gnomad AMR

AF:

0.832

Gnomad ASJ

AF:

0.767

Gnomad EAS

AF:

0.869

Gnomad SAS

AF:

0.815

Gnomad FIN

AF:

0.825

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.798

Gnomad OTH

AF:

0.826

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

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)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.850

AC:

129378

AN:

152248

Hom.:

55384

Cov.:

AF XY:

0.848

AC XY:

63135

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.962

AC:

39999

AN:

41572

American (AMR)

AF:

0.831

AC:

12720

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.767

AC:

2661

AN:

3470

East Asian (EAS)

AF:

0.869

AC:

4489

AN:

5168

South Asian (SAS)

AF:

0.813

AC:

3928

AN:

4832

European-Finnish (FIN)

AF:

0.825

AC:

8722

AN:

10574

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.798

AC:

54275

AN:

68018

Other (OTH)

AF:

0.826

AC:

1747

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

972

1945

2917

3890

4862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.811

Hom.:

155957

Bravo

AF:

0.855

Asia WGS

AF:

0.862

AC:

2996

AN:

3474

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

-0.94

CADD

Benign

0.38

(source)

DANN

Benign

0.32

PhyloP100

0.035

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