10-18003208-G-A

Variant names:

• chr10-18003208-G-A
• NM_001145195.2:c.1797G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001145195.2(SLC39A12):​c.1797G>A​(p.Met599Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03927669).
• BP6: Variant 10-18003208-G-A is Benign according to our data. Variant chr10-18003208-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3797758.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A12	NM_001145195.2	c.1797G>A	p.Met599Ile	missense_variant	Exon 12 of 13	ENST00000377369.7	NP_001138667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A12	ENST00000377369.7	c.1797G>A	p.Met599Ile	missense_variant	Exon 12 of 13	1	NM_001145195.2	ENSP00000366586.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461802 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 29, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.0
DANN	Benign	0.76
DEOGEN2	Benign	0.00077	.;T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.32	T;T;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.039	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.81	.;N;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.75	N;N;N;N
REVEL	Benign	0.089
Sift	Benign	0.19	T;T;T;T
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.0	.;B;B;B
Vest4		0.16
MutPred		0.48		.;Gain of methylation at K600 (P = 0.028);.;.;
MVP		0.030
MPC		0.024
ClinPred		0.079	T
GERP RS		-8.1
Varity_R		0.081
gMVP		0.045

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: chr10-18292137;