4-102267552-C-T

Variant names:

Variant summary

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

The NM_001135146.2(SLC39A8):c.1171G>A(p.Ala391Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 1,613,550 control chromosomes in the GnomAD database, including 3,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 223 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3511 hom. )

Consequence

SLC39A8
NM_001135146.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.82

Publications

608 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0029747784).

BP6

Variant 4-102267552-C-T is Benign according to our data. Variant chr4-102267552-C-T is described in ClinVar as Benign. ClinVar VariationId is 1271175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0688 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135146.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC39A8	NM_001135146.2	MANE Select	c.1171G>A	p.Ala391Thr	missense	Exon 8 of 9	NP_001128618.1	Q9C0K1-1
SLC39A8	NM_022154.5		c.1171G>A	p.Ala391Thr	missense	Exon 7 of 8	NP_071437.3	Q9C0K1-1
SLC39A8	NM_001135147.1		c.1171G>A	p.Ala391Thr	missense	Exon 8 of 11	NP_001128619.1	Q9C0K1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC39A8	ENST00000356736.5	TSL:1 MANE Select	c.1171G>A	p.Ala391Thr	missense	Exon 8 of 9	ENSP00000349174.4	Q9C0K1-1
SLC39A8	ENST00000394833.6	TSL:1	c.1171G>A	p.Ala391Thr	missense	Exon 7 of 8	ENSP00000378310.2	Q9C0K1-1
SLC39A8	ENST00000856304.1		c.1462G>A	p.Ala488Thr	missense	Exon 9 of 10	ENSP00000526363.1

Frequencies

GnomAD3 genomes

AF:

0.0447

AC:

6804

AN:

152048

Hom.:

223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0521

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00539

Gnomad FIN

AF:

0.00972

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0704

Gnomad OTH

AF:

0.0550

GnomAD2 exomes

AF:

0.0454

AC:

11388

AN:

250646

AF XY:

0.0458

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.0377

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.000708

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.0695

Gnomad OTH exome

AF:

0.0556

GnomAD4 exome

AF:

0.0636

AC:

92996

AN:

1461384

Hom.:

3511

Cov.:

AF XY:

0.0633

AC XY:

46027

AN XY:

726972

show subpopulations

African (AFR)

AF:

0.0115

AC:

384

AN:

33472

American (AMR)

AF:

0.0395

AC:

1762

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

3459

AN:

26124

East Asian (EAS)

AF:

0.000302

AC:

AN:

39682

South Asian (SAS)

AF:

0.00325

AC:

280

AN:

86190

European-Finnish (FIN)

AF:

0.0134

AC:

714

AN:

53370

Middle Eastern (MID)

AF:

0.0479

AC:

276

AN:

5768

European-Non Finnish (NFE)

AF:

0.0741

AC:

82332

AN:

1111742

Other (OTH)

AF:

0.0626

AC:

3777

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

4431

8862

13292

17723

22154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2960

5920

8880

11840

14800

<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:

0.0447

AC:

6802

AN:

152166

Hom.:

223

Cov.:

AF XY:

0.0426

AC XY:

3171

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0127

AC:

529

AN:

41498

American (AMR)

AF:

0.0521

AC:

796

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

416

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.00519

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00972

AC:

103

AN:

10592

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0704

AC:

4789

AN:

67996

Other (OTH)

AF:

0.0544

AC:

115

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

332

664

996

1328

1660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0671

Hom.:

2038

Bravo

AF:

0.0493

TwinsUK

AF:

0.0790

AC:

293

ALSPAC

AF:

0.0649

AC:

250

ESP6500AA

AF:

0.0154

AC:

ESP6500EA

AF:

0.0757

AC:

651

ExAC

AF:

0.0422

AC:

5121

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Inflammatory bowel disease 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.86

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

PhyloP100

1.8

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.1

REVEL

Benign

0.085

Sift

Benign

0.17

Sift4G

Uncertain

0.040

Polyphen

0.59

Vest4

0.26

MPC

1.1

ClinPred

0.046

GERP RS

4.4

Varity_R

0.20

gMVP

0.59

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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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