10-17981381-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001145195.2(SLC39A12):c.994G>A(p.Asp332Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,613,692 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (48 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (49 hom.)
• Consequence: SLC39A12 NM_001145195.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.12

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030641556).
• BP6: Variant 10-17981381-G-A is Benign according to our data. Variant chr10-17981381-G-A is described in ClinVar as [Benign]. Clinvar id is 781194.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2081/152192) while in subpopulation AFR AF= 0.0467 (1938/41512). AF 95% confidence interval is 0.045. There are 48 homozygotes in gnomad4. There are 930 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 48 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A12	NM_001145195.2	c.994G>A	p.Asp332Asn	missense_variant	6/13	ENST00000377369.7
SLC39A12	NM_001282733.2	c.994G>A	p.Asp332Asn	missense_variant	6/13
SLC39A12	NM_152725.4	c.994G>A	p.Asp332Asn	missense_variant	6/12
SLC39A12	NM_001282734.2	c.592G>A	p.Asp198Asn	missense_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A12	ENST00000377369.7	c.994G>A	p.Asp332Asn	missense_variant	6/13	1	NM_001145195.2	A1
SLC39A12	ENST00000377371.3	c.994G>A	p.Asp332Asn	missense_variant	6/13	1		P4
SLC39A12	ENST00000377374.8	c.994G>A	p.Asp332Asn	missense_variant	6/12	2
SLC39A12	ENST00000539911.5	c.592G>A	p.Asp198Asn	missense_variant	5/12	2

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2072 AN: 152074 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00351 AC: 881 AN: 251300 Hom.: 21 AF XY: 0.00248 AC XY: 337 AN XY: 135814

Gnomad AFR exome AF: 0.0470

Gnomad AMR exome AF: 0.00234

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00137 AC: 2001 AN: 1461500 Hom.: 49 Cov.: 31 AF XY: 0.00123 AC XY: 893 AN XY: 727048

Gnomad4 AFR exome AF: 0.0470

Gnomad4 AMR exome AF: 0.00264

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000944

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.0137 AC: 2081 AN: 152192 Hom.: 48 Cov.: 32 AF XY: 0.0125 AC XY: 930 AN XY: 74410

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.00668

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00290 Hom.: 12

Bravo AF: 0.0160

ESP6500AA AF: 0.0468 AC: 206

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00452 AC: 549

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	21
Dann	Benign	0.97
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.015
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.86	D;D;D;D
MetaRNN	Benign	0.0031	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.86	N;N;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.36	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.64	T;T;T;T
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.0090, 0.028, 0.016	.;B;B;B
Vest4		0.14
MVP		0.15
MPC		0.023
ClinPred		0.0035	T
GERP RS		2.8
Varity_R		0.034
gMVP		0.37

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: rs62618669; hg19: chr10-18270310;