4-102386392-A-C

Variant names:

• chr4-102386392-A-C
• rs1159788
• ENST00000502903.1:n.198-882T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000502903.1(SLC39A8):​n.198-882T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,960 control chromosomes in the GnomAD database, including 25,699 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (25699 hom., cov: 31)
• Consequence: SLC39A8 ENST00000502903.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 2 publications found

Genes affected

SLC39A8 (HGNC:20862): (solute carrier family 39 member 8) This gene encodes a member of the SLC39 family of solute-carrier genes, which show structural characteristics of zinc transporters. The encoded protein is glycosylated and found in the plasma membrane and mitochondria, and functions in the cellular import of zinc at the onset of inflammation. It is also thought to be the primary transporter of the toxic cation cadmium, which is found in cigarette smoke. Multiple transcript variants encoding different isoforms have been found for this gene. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Oct 2008]

SLC39A8 Gene-Disease associations (from GenCC):

• SLC39A8-CDG

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A8	ENST00000502903.1	n.198-882T>G		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84929 AN: 151842 Hom.: 25684 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.603

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.559 AC: 84967 AN: 151960 Hom.: 25699 Cov.: 31 AF XY: 0.558 AC XY: 41436 AN XY: 74292

African (AFR) AF: 0.342 AC: 14160 AN: 41436

American (AMR) AF: 0.545 AC: 8330 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2773 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1461 AN: 5164

South Asian (SAS) AF: 0.663 AC: 3196 AN: 4822

European-Finnish (FIN) AF: 0.616 AC: 6493 AN: 10546

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.683 AC: 46395 AN: 67934

Other (OTH) AF: 0.606 AC: 1277 AN: 2108

Alfa AF: 0.601 Hom.: 5017

Bravo AF: 0.543

Asia WGS AF: 0.473 AC: 1644 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.64
DANN	Benign	0.41
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1159788; hg19: chr4-103307549;