4-102253334-A-G

Position:

• chr4-102253334-A-G

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.*88T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 680,176 control chromosomes in the GnomAD database, including 113,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (30504 hom., cov: 29)
  • Exomes 𝑓: 0.55 (82501 hom.)
• Consequence: SLC39A8 NM_001135147.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.183

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 4-102253334-A-G is Benign according to our data. Variant chr4-102253334-A-G is described in ClinVar as [Benign]. Clinvar id is 1242026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A8	NM_001135147.1	c.*88T>C		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.*395T>C		non_coding_transcript_exon_variant	12/12	2		ENSP00000394548.3
SLC39A8	ENST00000424970.7	n.*395T>C		3_prime_UTR_variant	12/12	2		ENSP00000394548.3

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94217 AN: 151640 Hom.: 30465 Cov.: 29

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.551 AC: 291295 AN: 528418 Hom.: 82501 Cov.: 0 AF XY: 0.546 AC XY: 155841 AN XY: 285188

Gnomad4 AFR exome AF: 0.795

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.407

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.498

Gnomad4 NFE exome AF: 0.578

Gnomad4 OTH exome AF: 0.581

GnomAD4 genome AF: 0.621 AC: 94298 AN: 151758 Hom.: 30504 Cov.: 29 AF XY: 0.612 AC XY: 45375 AN XY: 74108

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.595

Alfa AF: 0.608 Hom.: 3602

Bravo AF: 0.639

Asia WGS AF: 0.418 AC: 1458 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	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	-0.90
CADD	Benign	1.6
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs151370; hg19: chr4-103174491; COSMIC: COSV70573952;