10-18043183-A-G

Variant names:

• chr10-18043183-A-G
• rs1935502
• NM_001145195.2:c.*350A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145195.2(SLC39A12):​c.*350A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 155,296 control chromosomes in the GnomAD database, including 46,394 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (45540 hom., cov: 33)
  • Exomes 𝑓: 0.73 (854 hom.)
• Consequence: SLC39A12 NM_001145195.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 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.*350A>G		3_prime_UTR	Exon 13 of 13	NP_001138667.1	Q504Y0-1
	SLC39A12	NM_001282733.2		c.*350A>G		3_prime_UTR	Exon 13 of 13	NP_001269662.1	Q504Y0-4
	SLC39A12	NM_152725.4		c.*350A>G		3_prime_UTR	Exon 12 of 12	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.*350A>G		3_prime_UTR	Exon 13 of 13	ENSP00000366586.2	Q504Y0-1
	SLC39A12	ENST00000377371.3	TSL:1	c.*350A>G		3_prime_UTR	Exon 13 of 13	ENSP00000366588.3	Q504Y0-4
	SLC39A12	ENST00000377374.8	TSL:2	c.*350A>G		3_prime_UTR	Exon 12 of 12	ENSP00000366591.4	Q504Y0-3

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116451 AN: 152026 Hom.: 45488 Cov.: 33

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.742

GnomAD4 exome AF: 0.731 AC: 2304 AN: 3152 Hom.: 854 Cov.: 1 AF XY: 0.726 AC XY: 1252 AN XY: 1724

African (AFR) AF: 0.944 AC: 85 AN: 90

American (AMR) AF: 0.679 AC: 57 AN: 84

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 65 AN: 100

East Asian (EAS) AF: 0.645 AC: 98 AN: 152

South Asian (SAS) AF: 0.480 AC: 49 AN: 102

European-Finnish (FIN) AF: 0.774 AC: 393 AN: 508

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.739 AC: 1439 AN: 1948

Other (OTH) AF: 0.701 AC: 115 AN: 164

GnomAD4 genome AF: 0.766 AC: 116555 AN: 152144 Hom.: 45540 Cov.: 33 AF XY: 0.764 AC XY: 56809 AN XY: 74382

African (AFR) AF: 0.911 AC: 37853 AN: 41540

American (AMR) AF: 0.664 AC: 10145 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2217 AN: 3466

East Asian (EAS) AF: 0.682 AC: 3538 AN: 5190

South Asian (SAS) AF: 0.497 AC: 2391 AN: 4814

European-Finnish (FIN) AF: 0.798 AC: 8428 AN: 10560

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.730 AC: 49592 AN: 67968

Other (OTH) AF: 0.745 AC: 1574 AN: 2114

Alfa AF: 0.734 Hom.: 114218

Bravo AF: 0.766

Asia WGS AF: 0.642 AC: 2231 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.48
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1935502; hg19: chr10-18332112; COSMIC: COSV66197391;