4-102253571-T-C

Position:

• chr4-102253571-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001135147.1(SLC39A8):​c.1327-141A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 458,388 control chromosomes in the GnomAD database, including 694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (308 hom., cov: 31)
  • Exomes 𝑓: 0.044 (386 hom.)
• Consequence: SLC39A8 NM_001135147.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-102253571-T-C is Benign according to our data. Variant chr4-102253571-T-C is described in ClinVar as [Benign]. Clinvar id is 1280996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A8	NM_001135147.1	c.1327-141A>G		intron_variant			NP_001128619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A8	ENST00000424970.7	n.*299-141A>G		intron_variant		2		ENSP00000394548.3

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8943 AN: 152126 Hom.: 307 Cov.: 31

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.0284

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0536

Gnomad OTH AF: 0.0536

GnomAD4 exome AF: 0.0442 AC: 13530 AN: 306144 Hom.: 386 AF XY: 0.0444 AC XY: 7046 AN XY: 158846

Gnomad4 AFR exome AF: 0.0938

Gnomad4 AMR exome AF: 0.0347

Gnomad4 ASJ exome AF: 0.0278

Gnomad4 EAS exome AF: 0.0000419

Gnomad4 SAS exome AF: 0.0325

Gnomad4 FIN exome AF: 0.0313

Gnomad4 NFE exome AF: 0.0519

Gnomad4 OTH exome AF: 0.0511

GnomAD4 genome AF: 0.0588 AC: 8953 AN: 152244 Hom.: 308 Cov.: 31 AF XY: 0.0563 AC XY: 4192 AN XY: 74458

Gnomad4 AFR AF: 0.0909

Gnomad4 AMR AF: 0.0514

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0300

Gnomad4 FIN AF: 0.0284

Gnomad4 NFE AF: 0.0536

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0571 Hom.: 23

Bravo AF: 0.0618

Asia WGS AF: 0.0200 AC: 68 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17032290; hg19: chr4-103174728;