4-102253268-T-C

Position:

• chr4-102253268-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.*154A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 444,508 control chromosomes in the GnomAD database, including 669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (306 hom., cov: 29)
  • Exomes 𝑓: 0.045 (363 hom.)
• Consequence: SLC39A8 NM_001135147.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.278

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 4-102253268-T-C is Benign according to our data. Variant chr4-102253268-T-C is described in ClinVar as [Benign]. Clinvar id is 1272653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A8	NM_001135147.1	c.*154A>G		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.*461A>G		non_coding_transcript_exon_variant	12/12	2		ENSP00000394548.3
SLC39A8	ENST00000424970.7	n.*461A>G		3_prime_UTR_variant	12/12	2		ENSP00000394548.3

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8925 AN: 151904 Hom.: 305 Cov.: 29

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.0286

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.0536

GnomAD4 exome AF: 0.0446 AC: 13056 AN: 292486 Hom.: 363 Cov.: 0 AF XY: 0.0451 AC XY: 6804 AN XY: 150924

Gnomad4 AFR exome AF: 0.0962

Gnomad4 AMR exome AF: 0.0337

Gnomad4 ASJ exome AF: 0.0278

Gnomad4 EAS exome AF: 0.0000857

Gnomad4 SAS exome AF: 0.0331

Gnomad4 FIN exome AF: 0.0307

Gnomad4 NFE exome AF: 0.0525

Gnomad4 OTH exome AF: 0.0506

GnomAD4 genome AF: 0.0588 AC: 8935 AN: 152022 Hom.: 306 Cov.: 29 AF XY: 0.0563 AC XY: 4181 AN XY: 74320

Gnomad4 AFR AF: 0.0908

Gnomad4 AMR AF: 0.0516

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0301

Gnomad4 FIN AF: 0.0286

Gnomad4 NFE AF: 0.0535

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0573 Hom.: 25

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	clinical testing	GeneDx	Sep 05, 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	2.2
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73836548; hg19: chr4-103174425;