4-102259718-C-T

Position:

• chr4-102259718-C-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.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

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=-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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A8	NM_001135147.1	c.1267-204G>A		intron_variant
SLC39A8	XM_024454184.2	c.1267-204G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A8	ENST00000424970.7	c.*239-204G>A		intron_variant, NMD_transcript_variant		2
SLC39A8	ENST00000682549.1	c.*239-204G>A		intron_variant, NMD_transcript_variant

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

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.703

Alfa AF: 0.738 Hom.: 5226

Bravo AF: 0.672

Asia WGS AF: 0.588 AC: 2043 AN: 3478

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	-1.0
CADD	Benign	0.35
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs189215; hg19: chr4-103180875;