10-18003293-T-C

Variant names:

• chr10-18003293-T-C
• rs1200311551
• NM_001145195.2:c.1882T>C

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.1882T>C​(p.Cys628Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19
• 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-AS1 (HGNC:44881): (SLC39A12 antisense RNA 1)

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=0.040803254).

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.1882T>C	p.Cys628Arg	missense	Exon 12 of 13	NP_001138667.1	Q504Y0-1
	SLC39A12	NM_001282733.2		c.1879T>C	p.Cys627Arg	missense	Exon 12 of 13	NP_001269662.1	Q504Y0-4
	SLC39A12	NM_152725.4		c.1771T>C	p.Cys591Arg	missense	Exon 11 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.1882T>C	p.Cys628Arg	missense	Exon 12 of 13	ENSP00000366586.2	Q504Y0-1
	SLC39A12	ENST00000377371.3	TSL:1	c.1879T>C	p.Cys627Arg	missense	Exon 12 of 13	ENSP00000366588.3	Q504Y0-4
	SLC39A12	ENST00000377374.8	TSL:2	c.1771T>C	p.Cys591Arg	missense	Exon 11 of 12	ENSP00000366591.4	Q504Y0-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251414 AF XY: 0.00

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: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461796 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727198

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53394

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111966

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

GnomAD4 genome Cov.: 32

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	0.072
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.7
DANN	Benign	0.71
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		1.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.026
Sift	Benign	0.50	T
Sift4G	Benign	0.52	T
Polyphen		0.0020	B
Vest4		0.35
MutPred		0.37		Loss of catalytic residue at P627 (P = 0.0131)
MVP		0.030
MPC		0.031
ClinPred		0.026	T
GERP RS		0.14
Varity_R		0.16
gMVP		0.46
Mutation Taster		=80/20	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: rs1200311551; hg19: chr10-18292222; COSMIC: COSV66202488;