10-17961683-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145195.2(SLC39A12):c.364A>G(p.Ile122Val) 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. 12/21 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)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16889763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A12	NM_001145195.2	c.364A>G	p.Ile122Val	missense_variant	3/13	ENST00000377369.7
SLC39A12	NM_001282733.2	c.364A>G	p.Ile122Val	missense_variant	3/13
SLC39A12	NM_152725.4	c.364A>G	p.Ile122Val	missense_variant	3/12
SLC39A12	NM_001282734.2	c.-39A>G		5_prime_UTR_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A12	ENST00000377369.7	c.364A>G	p.Ile122Val	missense_variant	3/13	1	NM_001145195.2	A1
SLC39A12	ENST00000377371.3	c.364A>G	p.Ile122Val	missense_variant	3/13	1		P4
SLC39A12	ENST00000377374.8	c.364A>G	p.Ile122Val	missense_variant	3/12	2
SLC39A12	ENST00000539911.5	c.-39A>G		5_prime_UTR_variant	2/12	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.364A>G (p.I122V) alteration is located in exon 3 (coding exon 2) of the SLC39A12 gene. This alteration results from a A to G substitution at nucleotide position 364, causing the isoleucine (I) at amino acid position 122 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0059	T;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;M
MutationTaster	Benign	0.97	D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.56	N;N;N
REVEL	Benign	0.046
Sift	Benign	0.087	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.81	P;P;P
Vest4		0.26
MutPred		0.33		Gain of catalytic residue at I122 (P = 0.3796);Gain of catalytic residue at I122 (P = 0.3796);Gain of catalytic residue at I122 (P = 0.3796);
MVP		0.088
MPC		0.030
ClinPred		0.56	D
GERP RS		3.1
Varity_R		0.056
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-18250612;