10-17961713-A-C

Variant names:

• chr10-17961713-A-C
• rs1281371726
• NM_001145195.2:c.394A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145195.2(SLC39A12):​c.394A>C​(p.Lys132Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K132E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18661058).

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.394A>C	p.Lys132Gln	missense	Exon 3 of 13	NP_001138667.1	Q504Y0-1
	SLC39A12	NM_001282733.2		c.394A>C	p.Lys132Gln	missense	Exon 3 of 13	NP_001269662.1	Q504Y0-4
	SLC39A12	NM_152725.4		c.394A>C	p.Lys132Gln	missense	Exon 3 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.394A>C	p.Lys132Gln	missense	Exon 3 of 13	ENSP00000366586.2	Q504Y0-1
	SLC39A12	ENST00000377371.3	TSL:1	c.394A>C	p.Lys132Gln	missense	Exon 3 of 13	ENSP00000366588.3	Q504Y0-4
	SLC39A12	ENST00000377374.8	TSL:2	c.394A>C	p.Lys132Gln	missense	Exon 3 of 12	ENSP00000366591.4	Q504Y0-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.9
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.081
Sift	Benign	0.24	T
Sift4G	Benign	0.35	T
Polyphen		0.98	D
Vest4		0.32
MutPred		0.26		Loss of ubiquitination at K132 (P = 0.0107)
MVP		0.088
MPC		0.096
ClinPred		0.81	D
GERP RS		5.3
Varity_R		0.15
gMVP		0.31
Mutation Taster		=87/13	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: rs1281371726; hg19: chr10-18250642;