rs2478568

Variant names:

• chr10-17978060-G-A
• rs2478568
• NM_001145195.2:c.910G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-17978060-G-A
• chr10-17978060-G-C

Variant summary

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

The NM_001145195.2(SLC39A12):​c.910G>A​(p.Val304Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,587,006 control chromosomes in the GnomAD database, including 332,722 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (31714 hom., cov: 33)
  • Exomes 𝑓: 0.65 (301008 hom.)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• Publications: 26 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 (MetaRNN=1.3368938E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.712 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.910G>A	p.Val304Ile	missense	Exon 5 of 13	NP_001138667.1	Q504Y0-1
	SLC39A12	NM_001282733.2		c.910G>A	p.Val304Ile	missense	Exon 5 of 13	NP_001269662.1	Q504Y0-4
	SLC39A12	NM_152725.4		c.910G>A	p.Val304Ile	missense	Exon 5 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.910G>A	p.Val304Ile	missense	Exon 5 of 13	ENSP00000366586.2	Q504Y0-1
	SLC39A12	ENST00000377371.3	TSL:1	c.910G>A	p.Val304Ile	missense	Exon 5 of 13	ENSP00000366588.3	Q504Y0-4
	SLC39A12	ENST00000377374.8	TSL:2	c.910G>A	p.Val304Ile	missense	Exon 5 of 12	ENSP00000366591.4	Q504Y0-3

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98023 AN: 151974 Hom.: 31677 Cov.: 33

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.643

GnomAD2 exomes AF: 0.657 AC: 152222 AN: 231600 AF XY: 0.660

Gnomad AFR exome AF: 0.624

Gnomad AMR exome AF: 0.682

Gnomad ASJ exome AF: 0.602

Gnomad EAS exome AF: 0.663

Gnomad FIN exome AF: 0.691

Gnomad NFE exome AF: 0.636

Gnomad OTH exome AF: 0.641

GnomAD4 exome AF: 0.646 AC: 927456 AN: 1434914 Hom.: 301008 Cov.: 34 AF XY: 0.648 AC XY: 462645 AN XY: 713418

African (AFR) AF: 0.633 AC: 20198 AN: 31902

American (AMR) AF: 0.677 AC: 26573 AN: 39256

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 15430 AN: 25396

East Asian (EAS) AF: 0.646 AC: 24840 AN: 38460

South Asian (SAS) AF: 0.729 AC: 59124 AN: 81066

European-Finnish (FIN) AF: 0.687 AC: 36258 AN: 52782

Middle Eastern (MID) AF: 0.675 AC: 3830 AN: 5678

European-Non Finnish (NFE) AF: 0.638 AC: 702584 AN: 1101066

Other (OTH) AF: 0.651 AC: 38619 AN: 59308

GnomAD4 genome AF: 0.645 AC: 98105 AN: 152092 Hom.: 31714 Cov.: 33 AF XY: 0.650 AC XY: 48301 AN XY: 74346

African (AFR) AF: 0.626 AC: 25963 AN: 41494

American (AMR) AF: 0.674 AC: 10313 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2105 AN: 3470

East Asian (EAS) AF: 0.665 AC: 3443 AN: 5176

South Asian (SAS) AF: 0.732 AC: 3533 AN: 4828

European-Finnish (FIN) AF: 0.691 AC: 7303 AN: 10566

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43259 AN: 67946

Other (OTH) AF: 0.648 AC: 1372 AN: 2116

Alfa AF: 0.638 Hom.: 154539

Bravo AF: 0.640

TwinsUK AF: 0.639 AC: 2370

ALSPAC AF: 0.653 AC: 2518

ESP6500AA AF: 0.626 AC: 2758

ESP6500EA AF: 0.632 AC: 5431

ExAC AF: 0.658 AC: 79916

Asia WGS AF: 0.725 AC: 2523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0010
DANN	Benign	0.40
DEOGEN2	Benign	0.00025	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.050	T
MetaRNN	Benign	0.0000013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.85	N
PhyloP100		-3.0
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.056
Sift	Benign	0.24	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.048
MPC		0.022
ClinPred		0.035	T
GERP RS		-9.4
Varity_R		0.042
gMVP		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2478568; hg19: chr10-18266989; COSMIC: COSV101070232;