chr1-219914602-C-T

Position:

• chr1-219914602-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000366926.4(SLC30A10):​c.*847G>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 0.00338 in 152,184 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SLC30A10 ENST00000366926.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.120

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC30A10	NM_018713.3	c.*847G>A		3_prime_UTR_variant	4/4	ENST00000366926.4	NP_061183.2
SLC30A10	NM_001376929.1	c.*847G>A		3_prime_UTR_variant	4/4		NP_001363858.1
SLC30A10	NM_001416004.1	c.*847G>A		3_prime_UTR_variant	3/3		NP_001402933.1
SLC30A10	NM_001416005.1	c.*847G>A		3_prime_UTR_variant	4/4		NP_001402934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC30A10	ENST00000366926.4	c.*847G>A		3_prime_UTR_variant	4/4	1	NM_018713.3	ENSP00000355893	P3

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 514 AN: 152066 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00368

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00549

Gnomad OTH AF: 0.00335

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: 0.00338 AC: 514 AN: 152184 Hom.: 2 Cov.: 33 AF XY: 0.00352 AC XY: 262 AN XY: 74394

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00368

Gnomad4 NFE AF: 0.00549

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00392 Hom.: 0

Bravo AF: 0.00275

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypermanganesemia with dystonia, polycythemia, and cirrhosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.8
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs143476893; hg19: chr1-220087944;