rs189215

Variant names:

• chr4-102259718-C-T
• rs189215
• ENST00000856287.1:c.*32-204G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001135147.1(SLC39A8):​c.1267-204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,084 control chromosomes in the GnomAD database, including 36,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (36884 hom., cov: 33)
• Consequence: SLC39A8 NM_001135147.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.673
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 4-102259718-C-T is Benign according to our data. Variant chr4-102259718-C-T is described in ClinVar as Benign. ClinVar VariationId is 1178719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135147.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	NM_001135147.1		c.1267-204G>A		intron	N/A	NP_001128619.1	Q9C0K1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	ENST00000856287.1		c.*32-204G>A		intron	N/A	ENSP00000526346.1
	SLC39A8	ENST00000424970.7	TSL:2	n.*239-204G>A		intron	N/A	ENSP00000394548.3	A0A804HKX2
	SLC39A8	ENST00000682549.1		n.*239-204G>A		intron	N/A	ENSP00000507483.1	A0A804HKX2

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104322 AN: 151966 Hom.: 36887 Cov.: 33

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.686 AC: 104343 AN: 152084 Hom.: 36884 Cov.: 33 AF XY: 0.683 AC XY: 50767 AN XY: 74362

African (AFR) AF: 0.528 AC: 21859 AN: 41428

American (AMR) AF: 0.642 AC: 9812 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2864 AN: 3468

East Asian (EAS) AF: 0.542 AC: 2796 AN: 5162

South Asian (SAS) AF: 0.764 AC: 3684 AN: 4822

European-Finnish (FIN) AF: 0.729 AC: 7724 AN: 10590

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53185 AN: 68002

Other (OTH) AF: 0.703 AC: 1486 AN: 2114

Alfa AF: 0.732 Hom.: 5349

Bravo AF: 0.672

Asia WGS AF: 0.588 AC: 2043 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.35
DANN	Benign	0.73
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs189215; hg19: chr4-103180875;