4-102283577-T-C

Position:

• chr4-102283577-T-C

Variant summary

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

The NM_001135146.2(SLC39A8):​c.841-15498A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 147,412 control chromosomes in the GnomAD database, including 40,936 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 0.75 (40936 hom., cov: 31)
• Consequence: SLC39A8 NM_001135146.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A8	NM_001135146.2	c.841-15498A>G		intron_variant		ENST00000356736.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A8	ENST00000356736.5	c.841-15498A>G		intron_variant		1	NM_001135146.2	P1

Frequencies

GnomAD3 genomes AF: 0.749 AC: 110255 AN: 147294 Hom.: 40890 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.730

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.749 AC: 110343 AN: 147412 Hom.: 40936 Cov.: 31 AF XY: 0.740 AC XY: 53127 AN XY: 71760

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.730

Gnomad4 OTH AF: 0.721

Alfa AF: 0.753 Hom.: 29417

Bravo AF: 0.771

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.68

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: rs233818; hg19: chr4-103204734;