10-17953442-C-T

Variant names:

• chr10-17953442-C-T
• rs781876660
• NM_001145195.2:c.166C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145195.2(SLC39A12):​c.166C>T​(p.Pro56Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.169
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047868043).

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.166C>T	p.Pro56Ser	missense	Exon 2 of 13	NP_001138667.1	Q504Y0-1
	SLC39A12	NM_001282733.2		c.166C>T	p.Pro56Ser	missense	Exon 2 of 13	NP_001269662.1	Q504Y0-4
	SLC39A12	NM_152725.4		c.166C>T	p.Pro56Ser	missense	Exon 2 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.166C>T	p.Pro56Ser	missense	Exon 2 of 13	ENSP00000366586.2	Q504Y0-1
	SLC39A12	ENST00000377371.3	TSL:1	c.166C>T	p.Pro56Ser	missense	Exon 2 of 13	ENSP00000366588.3	Q504Y0-4
	SLC39A12	ENST00000377374.8	TSL:2	c.166C>T	p.Pro56Ser	missense	Exon 2 of 12	ENSP00000366591.4	Q504Y0-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 250862 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1461894 Hom.: 0 Cov.: 34 AF XY: 0.0000316 AC XY: 23 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000306 AC: 34 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15266

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.21
DANN	Benign	0.46
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.17
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.061
Sift	Benign	1.0	T
Sift4G	Benign	0.42	T
Polyphen		0.014	B
Vest4		0.061
MutPred		0.14		Loss of catalytic residue at P56 (P = 0.0024)
MVP		0.014
MPC		0.023
ClinPred		0.039	T
GERP RS		-1.3
Varity_R		0.018
gMVP		0.40
Mutation Taster		=85/15	polymorphism

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: rs781876660; hg19: chr10-18242371;