rs142948678

Variant names:

• chr10-17953404-C-G
• rs142948678
• NM_001145195.2:c.128C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-17953404-C-G
• chr10-17953404-C-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.128C>G​(p.Pro43Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,152 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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=0.08160791).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A12	NM_001145195.2	c.128C>G	p.Pro43Arg	missense_variant	Exon 2 of 13	ENST00000377369.7	NP_001138667.1
SLC39A12	NM_001282733.2	c.128C>G	p.Pro43Arg	missense_variant	Exon 2 of 13		NP_001269662.1
SLC39A12	NM_152725.4	c.128C>G	p.Pro43Arg	missense_variant	Exon 2 of 12		NP_689938.2
SLC39A12	NM_001282734.2	c.-142+1379C>G		intron_variant	Intron 1 of 11		NP_001269663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A12	ENST00000377369.7	c.128C>G	p.Pro43Arg	missense_variant	Exon 2 of 13	1	NM_001145195.2	ENSP00000366586.2
SLC39A12	ENST00000377371.3	c.128C>G	p.Pro43Arg	missense_variant	Exon 2 of 13	1		ENSP00000366588.3
SLC39A12	ENST00000377374.8	c.128C>G	p.Pro43Arg	missense_variant	Exon 2 of 12	2		ENSP00000366591.4
SLC39A12	ENST00000539911.5	c.-142+1379C>G		intron_variant	Intron 1 of 11	2		ENSP00000440445.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74332

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Benign	0.20
DEOGEN2	Benign	0.0063	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.19	T;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.084
Sift	Benign	0.25	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.17
MutPred		0.28		Gain of methylation at P43 (P = 0.0365);Gain of methylation at P43 (P = 0.0365);Gain of methylation at P43 (P = 0.0365);
MVP		0.030
MPC		0.024
ClinPred		0.15	T
GERP RS		3.7
Varity_R		0.039
gMVP		0.62

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: rs142948678; hg19: chr10-18242333;