Genetic Variant SLC39A8:c.*258G>A (chr4-102253164-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001135147.1(SLC39A8):c.*258G>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 0.561 in 352,306 control chromosomes in the GnomAD database, including 55,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 22888 hom., cov: 26)

Exomes 𝑓: 0.56 ( 32687 hom. )

Consequence

SLC39A8
NM_001135147.1 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.97

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

SLC39A8-CDG
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

SLC39A8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 4-102253164-C-T is Benign according to our data. Variant chr4-102253164-C-T is described in ClinVar as Benign. ClinVar VariationId is 1247122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135147.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	NM_001135147.1		c.*258G>A		3_prime_UTR	Exon 11 of 11	NP_001128619.1	Q9C0K1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A8	ENST00000424970.7	TSL:2	n.*565G>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000394548.3	A0A804HKX2
	SLC39A8	ENST00000424970.7	TSL:2	n.*565G>A		3_prime_UTR	Exon 12 of 12	ENSP00000394548.3	A0A804HKX2

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

82447

AN:

148220

Hom.:

22865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.563

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.664

Gnomad EAS

AF:

0.452

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.510

Gnomad MID

AF:

0.635

Gnomad NFE

AF:

0.578

Gnomad OTH

AF:

0.556

GnomAD4 exome

AF:

0.564

AC:

115042

AN:

203970

Hom.:

32687

Cov.:

AF XY:

0.567

AC XY:

58795

AN XY:

103746

show subpopulations

African (AFR)

AF:

0.565

AC:

3415

AN:

6046

American (AMR)

AF:

0.511

AC:

3013

AN:

5898

Ashkenazi Jewish (ASJ)

AF:

0.671

AC:

5295

AN:

7896

East Asian (EAS)

AF:

0.409

AC:

7545

AN:

18468

South Asian (SAS)

AF:

0.440

AC:

1581

AN:

3596

European-Finnish (FIN)

AF:

0.515

AC:

8044

AN:

15616

Middle Eastern (MID)

AF:

0.581

AC:

974

AN:

1676

European-Non Finnish (NFE)

AF:

0.590

AC:

77268

AN:

130988

Other (OTH)

AF:

0.574

AC:

7907

AN:

13786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

2317

4634

6952

9269

11586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

294

588

882

1176

1470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.556

AC:

82506

AN:

148336

Hom.:

22888

Cov.:

AF XY:

0.550

AC XY:

39759

AN XY:

72288

show subpopulations

African (AFR)

AF:

0.564

AC:

22507

AN:

39928

American (AMR)

AF:

0.513

AC:

7633

AN:

14890

Ashkenazi Jewish (ASJ)

AF:

0.664

AC:

2279

AN:

3434

East Asian (EAS)

AF:

0.451

AC:

2284

AN:

5064

South Asian (SAS)

AF:

0.427

AC:

1946

AN:

4560

European-Finnish (FIN)

AF:

0.510

AC:

5176

AN:

10144

Middle Eastern (MID)

AF:

0.637

AC:

186

AN:

292

European-Non Finnish (NFE)

AF:

0.578

AC:

38762

AN:

67090

Other (OTH)

AF:

0.557

AC:

1137

AN:

2040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1800

3600

5401

7201

9001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.495

Hom.:

3014

Bravo

AF:

0.555

Asia WGS

AF:

0.402

AC:

1399

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.73

(source)

DANN

Benign

0.56

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over