4-102253152-C-T

Position:

• chr4-102253152-C-T

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.*270G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 326,126 control chromosomes in the GnomAD database, including 52,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (22888 hom., cov: 24)
  • Exomes 𝑓: 0.55 (29625 hom.)
• Consequence: SLC39A8 NM_001135147.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.226

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=-0.91).
• BP6: Variant 4-102253152-C-T is Benign according to our data. Variant chr4-102253152-C-T is described in ClinVar as [Benign]. Clinvar id is 1238663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A8	NM_001135147.1	c.*270G>A		3_prime_UTR_variant	11/11		NP_001128619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A8	ENST00000424970.7	n.*577G>A		non_coding_transcript_exon_variant	12/12	2		ENSP00000394548.3
SLC39A8	ENST00000424970.7	n.*577G>A		3_prime_UTR_variant	12/12	2		ENSP00000394548.3

Frequencies

GnomAD3 genomes AF: 0.599 AC: 82368 AN: 137598 Hom.: 22866 Cov.: 24

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.667

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.590

GnomAD4 exome AF: 0.553 AC: 104285 AN: 188424 Hom.: 29625 Cov.: 0 AF XY: 0.556 AC XY: 53275 AN XY: 95890

Gnomad4 AFR exome AF: 0.544

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.664

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.503

Gnomad4 NFE exome AF: 0.579

Gnomad4 OTH exome AF: 0.565

GnomAD4 genome AF: 0.599 AC: 82425 AN: 137702 Hom.: 22888 Cov.: 24 AF XY: 0.593 AC XY: 39692 AN XY: 66944

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.591

Alfa AF: 0.568 Hom.: 2982

Bravo AF: 0.555

Asia WGS AF: 0.407 AC: 1413 AN: 3464

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	clinical testing	GeneDx	Jul 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
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: rs151371; hg19: chr4-103174309;