1-219914361-C-T

Position:

• chr1-219914361-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.230

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 Benign. Variant got -14 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 id is 295576.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A10	NM_018713.3	c.*1088G>A		3_prime_UTR_variant	4/4	ENST00000366926.4
SLC30A10	NM_001376929.1	c.*1088G>A		3_prime_UTR_variant	4/4
SLC30A10	NM_001416004.1	c.*1088G>A		3_prime_UTR_variant	3/3
SLC30A10	NM_001416005.1	c.*1088G>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A10	ENST00000366926.4	c.*1088G>A		3_prime_UTR_variant	4/4	1	NM_018713.3	P3

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3108 AN: 152136 Hom.: 83 Cov.: 33

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: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0205 AC: 3117 AN: 152254 Hom.: 84 Cov.: 33 AF XY: 0.0224 AC XY: 1665 AN XY: 74430

Gnomad4 AFR AF: 0.00361

Gnomad4 AMR AF: 0.0455

Gnomad4 ASJ AF: 0.0182

Gnomad4 EAS AF: 0.0859

Gnomad4 SAS AF: 0.0593

Gnomad4 FIN AF: 0.00821

Gnomad4 NFE AF: 0.0196

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0185 Hom.: 34

Bravo AF: 0.0218

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypermanganesemia with dystonia, polycythemia, and cirrhosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.0
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2275706; hg19: chr1-220087703;