NM_001145195.2:c.262-7delT

Variant names:

• chr10-17961572-CT-C
• rs34494172
• NM_001145195.2:c.262-7delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001145195.2(SLC39A12):​c.262-7delT variant causes a splice region, 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, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.793
• Publications: 0 publications found

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]

SLC39A12 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145195.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A12	NM_001145195.2	MANE Select	c.262-7delT		splice_region intron	N/A	NP_001138667.1	Q504Y0-1
	SLC39A12	NM_001282733.2		c.262-7delT		splice_region intron	N/A	NP_001269662.1	Q504Y0-4
	SLC39A12	NM_152725.4		c.262-7delT		splice_region intron	N/A	NP_689938.2	Q504Y0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A12	ENST00000377369.7	TSL:1 MANE Select	c.262-8delT		splice_region intron	N/A	ENSP00000366586.2	Q504Y0-1
	SLC39A12	ENST00000377371.3	TSL:1	c.262-8delT		splice_region intron	N/A	ENSP00000366588.3	Q504Y0-4
	SLC39A12	ENST00000377374.8	TSL:2	c.262-8delT		splice_region intron	N/A	ENSP00000366591.4	Q504Y0-3

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

GnomAD2 exomes AF: 0.00528 AC: 1253 AN: 237246 AF XY: 0.00397

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 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

African (AFR) AF: 0.0761 AC: 2463 AN: 32370

American (AMR) AF: 0.00326 AC: 134 AN: 41158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25262

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.000146 AC: 12 AN: 82352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52894

Middle Eastern (MID) AF: 0.00475 AC: 23 AN: 4844

European-Non Finnish (NFE) AF: 0.000108 AC: 120 AN: 1106550

Other (OTH) AF: 0.00429 AC: 255 AN: 59470

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

African (AFR) AF: 0.0688 AC: 2855 AN: 41516

American (AMR) AF: 0.00536 AC: 82 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68018

Other (OTH) AF: 0.0137 AC: 29 AN: 2114

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34494172; hg19: chr10-18250501;