1-219914705-C-A

Variant names:

• chr1-219914705-C-A
• rs2275707
• NM_018713.3:c.*744G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0350

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A10	NM_018713.3	c.*744G>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000366926.4	NP_061183.2
SLC30A10	NM_001376929.1	c.*744G>T		3_prime_UTR_variant	Exon 4 of 4		NP_001363858.1
SLC30A10	NM_001416004.1	c.*744G>T		3_prime_UTR_variant	Exon 3 of 3		NP_001402933.1
SLC30A10	NM_001416005.1	c.*744G>T		3_prime_UTR_variant	Exon 4 of 4		NP_001402934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A10	ENST00000366926	c.*744G>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_018713.3	ENSP00000355893.4

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129280 AN: 152130 Hom.: 55341 Cov.: 32

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: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.850 AC: 129378 AN: 152248 Hom.: 55384 Cov.: 32 AF XY: 0.848 AC XY: 63135 AN XY: 74410

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.831

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.826

Alfa AF: 0.802 Hom.: 100224

Bravo AF: 0.855

Asia WGS AF: 0.862 AC: 2996 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hypermanganesemia with dystonia, polycythemia, and cirrhosis Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.38
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2275707; hg19: chr1-220088047;