Genetic Variant SLC30A10:p.Val98_Phe134del (chr1-219928038-GGAAGATGAGCAGCCCCACCACGTTGACCAACAGCCCCAGGACGCCGACGATGAGCACCAGCTCGGGGTCATCGATGCGCTCGGGCCGGGCCAGGCGCAGCACGGCCTCCAC-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM4PP3

The NM_018713.3(SLC30A10):c.292_402del(p.Val98_Phe134del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,433,684 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SLC30A10
NM_018713.3 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 8.79

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_018713.3.

PP3

No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A10	NM_018713.3 link	c.292_402del	p.Val98_Phe134del	conservative_inframe_deletion	Exon 1 of 4	ENST00000366926.4	NP_061183.2	Q6XR72-4B3KR19
SLC30A10	NM_001416005.1 link	c.-422_-312del		5_prime_UTR_variant	Exon 1 of 4		NP_001402934.1
SLC30A10	NM_001376929.1 link	c.452-1044_452-934del		intron_variant	Intron 1 of 3		NP_001363858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC30A10	ENST00000366926.4 link	c.292_402del	p.Val98_Phe134del	conservative_inframe_deletion	Exon 1 of 4	1	NM_018713.3	ENSP00000355893.4	Q6XR72-4
SLC30A10	ENST00000356609.2 link	n.292_402del		non_coding_transcript_exon_variant	Exon 1 of 4	1		ENSP00000349018.2	Q6XR72-3
SLC30A10	ENST00000696608.1 link	c.452-1044_452-934del		intron_variant	Intron 1 of 3			ENSP00000512752.1	A0A8Q3WLF3
SLC30A10	ENST00000484239.5 link	n.81-1044_81-934del		intron_variant	Intron 1 of 8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1433684

Hom.:

AF XY:

0.00000141

AC XY:

AN XY:

710832

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32360

American (AMR)

AF:

0.00

AC:

AN:

41768

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25630

East Asian (EAS)

AF:

0.00

AC:

AN:

37300

South Asian (SAS)

AF:

0.00

AC:

AN:

81972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49780

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1099848

Other (OTH)

AF:

0.00

AC:

AN:

59284

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

Hypermanganesemia with dystonia, polycythemia, and cirrhosis

Other:1

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

8.8

Mutation Taster

=7/193

disease causing (ClinVar)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over