10-17981405-A-G

Position:

• chr10-17981405-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.1018A>G​(p.Ile340Val) variant causes a missense change. 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: 5.64

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=0.25528532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A12	NM_001145195.2	c.1018A>G	p.Ile340Val	missense_variant	6/13	ENST00000377369.7	NP_001138667.1
SLC39A12	NM_001282733.2	c.1018A>G	p.Ile340Val	missense_variant	6/13		NP_001269662.1
SLC39A12	NM_152725.4	c.1018A>G	p.Ile340Val	missense_variant	6/12		NP_689938.2
SLC39A12	NM_001282734.2	c.616A>G	p.Ile206Val	missense_variant	5/12		NP_001269663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A12	ENST00000377369.7	c.1018A>G	p.Ile340Val	missense_variant	6/13	1	NM_001145195.2	ENSP00000366586	A1
SLC39A12	ENST00000377371.3	c.1018A>G	p.Ile340Val	missense_variant	6/13	1		ENSP00000366588	P4
SLC39A12	ENST00000377374.8	c.1018A>G	p.Ile340Val	missense_variant	6/12	2		ENSP00000366591
SLC39A12	ENST00000539911.5	c.616A>G	p.Ile206Val	missense_variant	5/12	2		ENSP00000440445

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 20, 2023

The c.1018A>G (p.I340V) alteration is located in exon 6 (coding exon 5) of the SLC39A12 gene. This alteration results from a A to G substitution at nucleotide position 1018, causing the isoleucine (I) at amino acid position 340 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	0.14
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0027	.;T;.;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.5	.;M;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.85	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.082	T;T;T;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.46, 0.78, 0.80	.;P;P;P
Vest4		0.33
MutPred		0.31		.;Loss of catalytic residue at L345 (P = 0.0337);Loss of catalytic residue at L345 (P = 0.0337);Loss of catalytic residue at L345 (P = 0.0337);
MVP		0.32
MPC		0.071
ClinPred		0.94	D
GERP RS		4.7
Varity_R		0.12
gMVP		0.28

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: chr10-18270334;