Variant 4-102253496-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001135147.1(SLC39A8):c.1327-66A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 684,240 control chromosomes in the GnomAD database, including 312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 46 hom., cov: 32)

Exomes 𝑓: 0.027 ( 266 hom. )

Consequence

SLC39A8
NM_001135147.1 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0110

Variant links:

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]

SLC39A8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-102253496-T-G is Benign according to our data. Variant chr4-102253496-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1188541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A8	NM_001135147.1 linkuse as main transcript	c.1327-66A>C		intron_variant			NP_001128619.1	Q9C0K1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A8	ENST00000424970.7 linkuse as main transcript	n.*299-66A>C		intron_variant		2		ENSP00000394548.3		A0A804HKX2

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3357

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0271

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.0632

Gnomad SAS

AF:

0.0238

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0268

Gnomad OTH

AF:

0.0220

GnomAD4 exome

AF:

0.0266

AC:

14151

AN:

531922

Hom.:

266

AF XY:

0.0268

AC XY:

7688

AN XY:

287352

show subpopulations

Gnomad4 AFR exome

AF:

0.00970

Gnomad4 AMR exome

AF:

0.0192

Gnomad4 ASJ exome

AF:

0.0115

Gnomad4 EAS exome

AF:

0.0675

Gnomad4 SAS exome

AF:

0.0241

Gnomad4 FIN exome

AF:

0.0221

Gnomad4 NFE exome

AF:

0.0265

Gnomad4 OTH exome

AF:

0.0223

GnomAD4 genome

AF:

0.0220

AC:

3356

AN:

152318

Hom.:

Cov.:

AF XY:

0.0215

AC XY:

1605

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0100

Gnomad4 AMR

AF:

0.0271

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.0641

Gnomad4 SAS

AF:

0.0234

Gnomad4 FIN

AF:

0.0170

Gnomad4 NFE

AF:

0.0267

Gnomad4 OTH

AF:

0.0217

Alfa

AF:

0.0166

Hom.:

Bravo

AF:

0.0215

Asia WGS

AF:

0.0370

AC:

128

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.0

DANN

Benign

0.55

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over