rs11382393

Variant names:

• chr4-102253159-C-CG
• rs11382393
• NM_001135147.1:c.*262dupC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001135147.1(SLC39A8):​c.*262dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.81 (50076 hom., cov: 0)
  • Exomes 𝑓: 0.76 (57681 hom.)
• Consequence: SLC39A8 NM_001135147.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.96
• 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 -10 ACMG points.

• BP6: Variant 4-102253159-C-CG is Benign according to our data. Variant chr4-102253159-C-CG is described in ClinVar as Benign. ClinVar VariationId is 1247560.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 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.*262dupC		3_prime_UTR	Exon 11 of 11	NP_001128619.1	Q9C0K1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	ENST00000424970.7	TSL:2	n.*569dupC		non_coding_transcript_exon	Exon 12 of 12	ENSP00000394548.3	A0A804HKX2
	SLC39A8	ENST00000424970.7	TSL:2	n.*569dupC		3_prime_UTR	Exon 12 of 12	ENSP00000394548.3	A0A804HKX2

Frequencies

GnomAD3 genomes AF: 0.809 AC: 121463 AN: 150048 Hom.: 50027 Cov.: 0

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.828

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.784

GnomAD4 exome AF: 0.762 AC: 148517 AN: 194824 Hom.: 57681 Cov.: 0 AF XY: 0.765 AC XY: 75748 AN XY: 98962

African (AFR) AF: 0.956 AC: 5760 AN: 6022

American (AMR) AF: 0.666 AC: 3759 AN: 5642

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 6446 AN: 7642

East Asian (EAS) AF: 0.507 AC: 9003 AN: 17764

South Asian (SAS) AF: 0.775 AC: 2626 AN: 3390

European-Finnish (FIN) AF: 0.734 AC: 10518 AN: 14320

Middle Eastern (MID) AF: 0.805 AC: 1239 AN: 1540

European-Non Finnish (NFE) AF: 0.790 AC: 98865 AN: 125202

Other (OTH) AF: 0.774 AC: 10301 AN: 13302

GnomAD4 genome AF: 0.809 AC: 121555 AN: 150166 Hom.: 50076 Cov.: 0 AF XY: 0.802 AC XY: 58688 AN XY: 73154

African (AFR) AF: 0.954 AC: 38828 AN: 40708

American (AMR) AF: 0.688 AC: 10332 AN: 15018

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2866 AN: 3444

East Asian (EAS) AF: 0.544 AC: 2765 AN: 5086

South Asian (SAS) AF: 0.770 AC: 3591 AN: 4666

European-Finnish (FIN) AF: 0.729 AC: 7504 AN: 10288

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53092 AN: 67688

Other (OTH) AF: 0.785 AC: 1627 AN: 2072

Alfa AF: 0.807 Hom.: 5363

Asia WGS AF: 0.624 AC: 2171 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
PhyloP100		-4.0
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: rs11382393; hg19: chr4-103174316;