10-17978007-A-G

Variant names:

• chr10-17978007-A-G
• rs149571343
• NM_001145195.2:c.857A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145195.2(SLC39A12):​c.857A>G​(p.Gln286Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.804

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048209727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A12	NM_001145195.2	c.857A>G	p.Gln286Arg	missense_variant	Exon 5 of 13	ENST00000377369.7	NP_001138667.1
SLC39A12	NM_001282733.2	c.857A>G	p.Gln286Arg	missense_variant	Exon 5 of 13		NP_001269662.1
SLC39A12	NM_152725.4	c.857A>G	p.Gln286Arg	missense_variant	Exon 5 of 12		NP_689938.2
SLC39A12	NM_001282734.2	c.455A>G	p.Gln152Arg	missense_variant	Exon 4 of 12		NP_001269663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A12	ENST00000377369.7	c.857A>G	p.Gln286Arg	missense_variant	Exon 5 of 13	1	NM_001145195.2	ENSP00000366586.2
SLC39A12	ENST00000377371.3	c.857A>G	p.Gln286Arg	missense_variant	Exon 5 of 13	1		ENSP00000366588.3
SLC39A12	ENST00000377374.8	c.857A>G	p.Gln286Arg	missense_variant	Exon 5 of 12	2		ENSP00000366591.4
SLC39A12	ENST00000539911.5	c.455A>G	p.Gln152Arg	missense_variant	Exon 4 of 12	2		ENSP00000440445.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.70
DANN	Benign	0.25
DEOGEN2	Benign	0.00041	.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.34	T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.048	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	.;N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.18	N;N;N;N
REVEL	Benign	0.079
Sift	Benign	0.54	T;T;T;T
Sift4G	Benign	0.55	T;T;T;T
Polyphen		0.0010, 0.0	.;B;B;B
Vest4		0.011
MutPred		0.14		.;Gain of phosphorylation at S289 (P = 0.068);Gain of phosphorylation at S289 (P = 0.068);Gain of phosphorylation at S289 (P = 0.068);
MVP		0.040
MPC		0.024
ClinPred		0.093	T
GERP RS		-0.31
Varity_R		0.026
gMVP		0.26

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: rs149571343; hg19: chr10-18266936;