rs233804

Variant names:

• chr4-102291759-C-A
• rs233804
• NM_001135146.2:c.840+12558G>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.840+12558G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,666 control chromosomes in the GnomAD database, including 5,620 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 0.27 (5620 hom., cov: 31)
• Consequence: SLC39A8 NM_001135146.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135146.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	NM_001135146.2	MANE Select	c.840+12558G>T		intron	N/A	NP_001128618.1
	SLC39A8	NM_022154.5		c.840+12558G>T		intron	N/A	NP_071437.3
	SLC39A8	NM_001135147.1		c.840+12558G>T		intron	N/A	NP_001128619.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	ENST00000356736.5	TSL:1 MANE Select	c.840+12558G>T		intron	N/A	ENSP00000349174.4
	SLC39A8	ENST00000394833.6	TSL:1	c.840+12558G>T		intron	N/A	ENSP00000378310.2
	SLC39A8	ENST00000682227.1		c.840+12558G>T		intron	N/A	ENSP00000508363.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40203 AN: 151548 Hom.: 5612 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.0862

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.265 AC: 40240 AN: 151666 Hom.: 5620 Cov.: 31 AF XY: 0.261 AC XY: 19313 AN XY: 74124

African (AFR) AF: 0.210 AC: 8706 AN: 41376

American (AMR) AF: 0.212 AC: 3224 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3468

East Asian (EAS) AF: 0.0856 AC: 440 AN: 5140

South Asian (SAS) AF: 0.353 AC: 1699 AN: 4814

European-Finnish (FIN) AF: 0.241 AC: 2529 AN: 10500

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21598 AN: 67848

Other (OTH) AF: 0.266 AC: 560 AN: 2104

Alfa AF: 0.312 Hom.: 3766

Bravo AF: 0.260

Asia WGS AF: 0.243 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.46
PhyloP100		-0.0060
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs233804; hg19: chr4-103212916;