4-102283688-C-A

Variant names:

• chr4-102283688-C-A
• rs233817
• NM_001135146.2:c.841-15609G>T

Variant summary

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

The NM_001135146.2(SLC39A8):​c.841-15609G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,098 control chromosomes in the GnomAD database, including 4,446 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 0.22 (4446 hom., cov: 33)
• Consequence: SLC39A8 NM_001135146.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A8	NM_001135146.2	c.841-15609G>T		intron_variant	Intron 6 of 8	ENST00000356736.5	NP_001128618.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A8	ENST00000356736.5	c.841-15609G>T		intron_variant	Intron 6 of 8	1	NM_001135146.2	ENSP00000349174.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34086 AN: 151980 Hom.: 4443 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.224 AC: 34102 AN: 152098 Hom.: 4446 Cov.: 33 AF XY: 0.224 AC XY: 16624 AN XY: 74332

African (AFR) AF: 0.105 AC: 4361 AN: 41510

American (AMR) AF: 0.185 AC: 2831 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1019 AN: 3470

East Asian (EAS) AF: 0.111 AC: 575 AN: 5186

South Asian (SAS) AF: 0.268 AC: 1293 AN: 4824

European-Finnish (FIN) AF: 0.297 AC: 3131 AN: 10540

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20034 AN: 67974

Other (OTH) AF: 0.232 AC: 490 AN: 2112

Alfa AF: 0.241 Hom.: 719

Bravo AF: 0.210

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.71
DANN	Benign	0.38
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs233817; hg19: chr4-103204845;