rs192068

Positions:

• chr4-102253662-G-A
• chr4-102253662-G-C
• chr4-102253662-G-T

Variant summary

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

The NM_001135147.1(SLC39A8):​c.1327-232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,332 control chromosomes in the GnomAD database, including 23,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.55 (23105 hom., cov: 30)
• Consequence: SLC39A8 NM_001135147.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.315

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=-0.92).
• BP6: Variant 4-102253662-G-A is Benign according to our data. Variant chr4-102253662-G-A is described in ClinVar as [Benign]. Clinvar id is 1238127.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A8	NM_001135147.1	c.1327-232C>T		intron_variant			NP_001128619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A8	ENST00000424970.7	c.*299-232C>T		intron_variant, NMD_transcript_variant		2		ENSP00000394548

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83213 AN: 151214 Hom.: 23083 Cov.: 30

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.635

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.550 AC: 83271 AN: 151332 Hom.: 23105 Cov.: 30 AF XY: 0.544 AC XY: 40206 AN XY: 73852

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.550

Alfa AF: 0.562 Hom.: 13367

Bravo AF: 0.555

Asia WGS AF: 0.404 AC: 1408 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs192068; hg19: chr4-103174819;