10-17961572-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001145195.2(SLC39A12):c.262-7del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,596,652 control chromosomes in the GnomAD database, including 177 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (87 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (90 hom.)
• Consequence: SLC39A12 NM_001145195.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.793

Genes affected

SLC39A12 (HGNC:20860): (solute carrier family 39 member 12) Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A12 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).[supplied by OMIM, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-17961572-CT-C is Benign according to our data. Variant chr10-17961572-CT-C is described in ClinVar as [Benign]. Clinvar id is 770588.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A12	NM_001145195.2	c.262-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000377369.7
SLC39A12	NM_001282733.2	c.262-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
SLC39A12	NM_001282734.2	c.-141-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
SLC39A12	NM_152725.4	c.262-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A12	ENST00000377369.7	c.262-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001145195.2	A1
SLC39A12	ENST00000377371.3	c.262-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		P4
SLC39A12	ENST00000377374.8	c.262-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2
SLC39A12	ENST00000539911.5	c.-141-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2977 AN: 152104 Hom.: 87 Cov.: 32

Gnomad AFR AF: 0.0688

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00528 AC: 1253 AN: 237246 Hom.: 40 AF XY: 0.00397 AC XY: 509 AN XY: 128184

Gnomad AFR exome AF: 0.0717

Gnomad AMR exome AF: 0.00267

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000223

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000192

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00208 AC: 3007 AN: 1444430 Hom.: 90 Cov.: 31 AF XY: 0.00182 AC XY: 1308 AN XY: 717588

Gnomad4 AFR exome AF: 0.0761

Gnomad4 AMR exome AF: 0.00326

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000146

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000108

Gnomad4 OTH exome AF: 0.00429

GnomAD4 genome AF: 0.0196 AC: 2986 AN: 152222 Hom.: 87 Cov.: 32 AF XY: 0.0190 AC XY: 1412 AN XY: 74432

Gnomad4 AFR AF: 0.0688

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0107 Hom.: 5

Bravo AF: 0.0217

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34494172; hg19: chr10-18250501;