rs10014145

Positions:

• chr4-102279420-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001135146.2(SLC39A8):​c.841-11341T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,968 control chromosomes in the GnomAD database, including 7,671 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7671 hom., cov: 31)
• Consequence: SLC39A8 NM_001135146.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.217

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A8	NM_001135146.2	c.841-11341T>C		intron_variant		ENST00000356736.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A8	ENST00000356736.5	c.841-11341T>C		intron_variant		1	NM_001135146.2	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47306 AN: 151850 Hom.: 7664 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.312 AC: 47343 AN: 151968 Hom.: 7671 Cov.: 31 AF XY: 0.309 AC XY: 22947 AN XY: 74278

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.291

Alfa AF: 0.319 Hom.: 10998

Bravo AF: 0.306

Asia WGS AF: 0.241 AC: 838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.3
DANN	Benign	0.60

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: rs10014145; hg19: chr4-103200577;