1-219915458-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_018713.3(SLC30A10):c.1449G>T(p.Thr483=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T483T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC30A10 NM_018713.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.59

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-219915458-C-A is Benign according to our data. Variant chr1-219915458-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1653791.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.59 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A10	NM_018713.3	c.1449G>T	p.Thr483=	synonymous_variant	4/4	ENST00000366926.4
SLC30A10	NM_001376929.1	c.1260G>T	p.Thr420=	synonymous_variant	4/4
SLC30A10	NM_001416004.1	c.774G>T	p.Thr258=	synonymous_variant	3/3
SLC30A10	NM_001416005.1	c.774G>T	p.Thr258=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A10	ENST00000366926.4	c.1449G>T	p.Thr483=	synonymous_variant	4/4	1	NM_018713.3	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000800 AC: 2 AN: 250086 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135080

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000659

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460746 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726594

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000349

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.099
Dann	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs148203711; hg19: chr1-220088800;