rs1935502

Positions:

• chr10-18043183-A-G
• chr10-18043183-A-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A12	NM_001145195.2	c.*350A>G		3_prime_UTR_variant	13/13	ENST00000377369.7	NP_001138667.1
SLC39A12	NM_001282733.2	c.*350A>G		3_prime_UTR_variant	13/13		NP_001269662.1
SLC39A12	NM_001282734.2	c.*350A>G		3_prime_UTR_variant	12/12		NP_001269663.1
SLC39A12	NM_152725.4	c.*350A>G		3_prime_UTR_variant	12/12		NP_689938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A12	ENST00000377369.7	c.*350A>G		3_prime_UTR_variant	13/13	1	NM_001145195.2	ENSP00000366586	A1
SLC39A12	ENST00000377371.3	c.*350A>G		3_prime_UTR_variant	13/13	1		ENSP00000366588	P4
SLC39A12	ENST00000377374.8	c.*350A>G		3_prime_UTR_variant	12/12	2		ENSP00000366591
SLC39A12	ENST00000539911.5	c.*350A>G		3_prime_UTR_variant	12/12	2		ENSP00000440445

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

Gnomad4 AFR exome AF: 0.944

Gnomad4 AMR exome AF: 0.679

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.645

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.774

Gnomad4 NFE exome AF: 0.739

Gnomad4 OTH exome AF: 0.701

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

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.745

Alfa AF: 0.730 Hom.: 45631

Bravo AF: 0.766

Asia WGS AF: 0.642 AC: 2231 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.48

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