10-17953355-G-T

Position:

• chr10-17953355-G-T

Variant summary

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

The NM_001145195.2(SLC39A12):​c.79G>T​(p.Asp27Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57

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=0.10243863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A12	NM_001145195.2	c.79G>T	p.Asp27Tyr	missense_variant	2/13	ENST00000377369.7	NP_001138667.1
SLC39A12	NM_001282733.2	c.79G>T	p.Asp27Tyr	missense_variant	2/13		NP_001269662.1
SLC39A12	NM_152725.4	c.79G>T	p.Asp27Tyr	missense_variant	2/12		NP_689938.2
SLC39A12	NM_001282734.2	c.-142+1330G>T		intron_variant			NP_001269663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A12	ENST00000377369.7	c.79G>T	p.Asp27Tyr	missense_variant	2/13	1	NM_001145195.2	ENSP00000366586	A1
SLC39A12	ENST00000377371.3	c.79G>T	p.Asp27Tyr	missense_variant	2/13	1		ENSP00000366588	P4
SLC39A12	ENST00000377374.8	c.79G>T	p.Asp27Tyr	missense_variant	2/12	2		ENSP00000366591
SLC39A12	ENST00000539911.5	c.-142+1330G>T		intron_variant		2		ENSP00000440445

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Mar 18, 2024

The c.79G>T (p.D27Y) alteration is located in exon 2 (coding exon 1) of the SLC39A12 gene. This alteration results from a G to T substitution at nucleotide position 79, causing the aspartic acid (D) at amino acid position 27 to be replaced by a tyrosine (Y). 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	0.090
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0055	T;.;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.011	D;D;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		0.57	P;P;P
Vest4		0.24
MutPred		0.13		Loss of disorder (P = 0.0216);Loss of disorder (P = 0.0216);Loss of disorder (P = 0.0216);
MVP		0.055
MPC		0.051
ClinPred		0.30	T
GERP RS		4.1
Varity_R		0.099
gMVP		0.36

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: rs1834453522; hg19: chr10-18242284;