rs1281371726

Variant names:

• chr10-17961713-A-C
• rs1281371726
• NM_001145195.2:c.394A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-17961713-A-C
• chr10-17961713-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.394A>C​(p.Lys132Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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=0.18661058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A12	NM_001145195.2	c.394A>C	p.Lys132Gln	missense_variant	Exon 3 of 13	ENST00000377369.7	NP_001138667.1
SLC39A12	NM_001282733.2	c.394A>C	p.Lys132Gln	missense_variant	Exon 3 of 13		NP_001269662.1
SLC39A12	NM_152725.4	c.394A>C	p.Lys132Gln	missense_variant	Exon 3 of 12		NP_689938.2
SLC39A12	NM_001282734.2	c.-9A>C		5_prime_UTR_variant	Exon 2 of 12		NP_001269663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A12	ENST00000377369.7	c.394A>C	p.Lys132Gln	missense_variant	Exon 3 of 13	1	NM_001145195.2	ENSP00000366586.2
SLC39A12	ENST00000377371.3	c.394A>C	p.Lys132Gln	missense_variant	Exon 3 of 13	1		ENSP00000366588.3
SLC39A12	ENST00000377374.8	c.394A>C	p.Lys132Gln	missense_variant	Exon 3 of 12	2		ENSP00000366591.4
SLC39A12	ENST00000539911	c.-9A>C		5_prime_UTR_variant	Exon 2 of 12	2		ENSP00000440445.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.85	N;N;N
REVEL	Benign	0.081
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.98	D;D;D
Vest4		0.32
MutPred		0.26		Loss of ubiquitination at K132 (P = 0.0107);Loss of ubiquitination at K132 (P = 0.0107);Loss of ubiquitination at K132 (P = 0.0107);
MVP		0.088
MPC		0.096
ClinPred		0.81	D
GERP RS		5.3
Varity_R		0.15
gMVP		0.31

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: rs1281371726; hg19: chr10-18250642;