4-102262907-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001135146.2(SLC39A8):c.*137G>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 0.0152 in 1,409,510 control chromosomes in the GnomAD database, including 2,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (1375 hom., cov: 33)
  • Exomes 𝑓: 0.0081 (1064 hom.)
• Consequence: SLC39A8 NM_001135146.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.206

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-102262907-C-T is Benign according to our data. Variant chr4-102262907-C-T is described in ClinVar as [Benign]. Clinvar id is 1269086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A8	NM_001135146.2	c.*137G>A		3_prime_UTR_variant	9/9	ENST00000356736.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A8	ENST00000356736.5	c.*137G>A		3_prime_UTR_variant	9/9	1	NM_001135146.2	P1

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11271 AN: 152102 Hom.: 1374 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0289

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00207

Gnomad OTH AF: 0.0507

GnomAD4 exome AF: 0.00808 AC: 10160 AN: 1257290 Hom.: 1064 Cov.: 31 AF XY: 0.00731 AC XY: 4447 AN XY: 608752

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.0215

Gnomad4 ASJ exome AF: 0.00644

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000950

Gnomad4 FIN exome AF: 0.000472

Gnomad4 NFE exome AF: 0.00130

Gnomad4 OTH exome AF: 0.0184

GnomAD4 genome AF: 0.0742 AC: 11291 AN: 152220 Hom.: 1375 Cov.: 33 AF XY: 0.0714 AC XY: 5315 AN XY: 74438

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.0289

Gnomad4 ASJ AF: 0.00750

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00207

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0171 Hom.: 227

Bravo AF: 0.0849

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.5
Dann	Benign	0.61

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: rs1045155; hg19: chr4-103184064;