4-102262932-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001135146.2(SLC39A8):c.*112T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 1,430,610 control chromosomes in the GnomAD database, including 423,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (40514 hom., cov: 33)
  • Exomes 𝑓: 0.77 (383305 hom.)
• Consequence: SLC39A8 NM_001135146.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.00

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-102262932-A-G is Benign according to our data. Variant chr4-102262932-A-G is described in ClinVar as [Benign]. Clinvar id is 1178220.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A8	NM_001135146.2	c.*112T>C		3_prime_UTR_variant	9/9	ENST00000356736.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A8	ENST00000356736.5	c.*112T>C		3_prime_UTR_variant	9/9	1	NM_001135146.2	P1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110360 AN: 151944 Hom.: 40503 Cov.: 33

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.728

GnomAD4 exome AF: 0.772 AC: 987418 AN: 1278548 Hom.: 383305 Cov.: 33 AF XY: 0.774 AC XY: 480799 AN XY: 621396

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.841

Gnomad4 EAS exome AF: 0.516

Gnomad4 SAS exome AF: 0.767

Gnomad4 FIN exome AF: 0.735

Gnomad4 NFE exome AF: 0.788

Gnomad4 OTH exome AF: 0.753

GnomAD4 genome AF: 0.726 AC: 110410 AN: 152062 Hom.: 40514 Cov.: 33 AF XY: 0.722 AC XY: 53630 AN XY: 74320

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.729

Alfa AF: 0.763 Hom.: 29855

Bravo AF: 0.717

Asia WGS AF: 0.603 AC: 2094 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.6
Dann	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs151393; hg19: chr4-103184089;