rs1047626

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_006345.4(SLC30A9):c.148A>G(p.Met50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,594,804 control chromosomes in the GnomAD database, including 452,076 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M50L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.61 ( 33665 hom., cov: 31)

Exomes 𝑓: 0.75 ( 418411 hom. )

Consequence

SLC30A9
NM_006345.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.01

Publications

58 publications found

Variant links:

Genes affected

SLC30A9 (HGNC:1329): (solute carrier family 30 member 9) Predicted to enable nuclear receptor coactivator activity. Involved in cellular zinc ion homeostasis and zinc ion transport. Located in several cellular components, including cytoplasmic vesicle; cytoskeleton; and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

SLC30A9 Gene-Disease associations (from GenCC):

psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Ambry Genetics

SLC30A9 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=1.2667841E-6).

BP6

Variant 4-42001654-A-G is Benign according to our data. Variant chr4-42001654-A-G is described in ClinVar as Benign. ClinVar VariationId is 1333130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006345.4. 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
	SLC30A9	NM_006345.4	MANE Select	c.148A>G	p.Met50Val	missense	Exon 2 of 18	NP_006336.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC30A9	ENST00000264451.12	TSL:1 MANE Select	c.148A>G	p.Met50Val	missense	Exon 2 of 18	ENSP00000264451.6	Q6PML9
SLC30A9	ENST00000866307.1		c.148A>G	p.Met50Val	missense	Exon 2 of 18	ENSP00000536366.1
SLC30A9	ENST00000962779.1		c.148A>G	p.Met50Val	missense	Exon 2 of 18	ENSP00000632838.1

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93324

AN:

151736

Hom.:

33656

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.913

Gnomad AMR

AF:

0.740

Gnomad ASJ

AF:

0.707

Gnomad EAS

AF:

0.954

Gnomad SAS

AF:

0.775

Gnomad FIN

AF:

0.801

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.759

Gnomad OTH

AF:

0.635

GnomAD2 exomes

AF:

0.748

AC:

183161

AN:

244750

AF XY:

0.757

show subpopulations

Gnomad AFR exome

AF:

0.193

Gnomad AMR exome

AF:

0.808

Gnomad ASJ exome

AF:

0.710

Gnomad EAS exome

AF:

0.960

Gnomad FIN exome

AF:

0.797

Gnomad NFE exome

AF:

0.763

Gnomad OTH exome

AF:

0.753

GnomAD4 exome

AF:

0.755

AC:

1089280

AN:

1442950

Hom.:

418411

Cov.:

AF XY:

0.756

AC XY:

542854

AN XY:

718360

show subpopulations

African (AFR)

AF:

0.188

AC:

6199

AN:

32942

American (AMR)

AF:

0.799

AC:

34207

AN:

42804

Ashkenazi Jewish (ASJ)

AF:

0.711

AC:

18357

AN:

25814

East Asian (EAS)

AF:

0.961

AC:

37863

AN:

39388

South Asian (SAS)

AF:

0.779

AC:

65595

AN:

84198

European-Finnish (FIN)

AF:

0.790

AC:

42124

AN:

53302

Middle Eastern (MID)

AF:

0.679

AC:

3888

AN:

5726

European-Non Finnish (NFE)

AF:

0.762

AC:

837657

AN:

1099088

Other (OTH)

AF:

0.727

AC:

43390

AN:

59688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

10613

21226

31840

42453

53066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20032

40064

60096

80128

100160

<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:

0.615

AC:

93343

AN:

151854

Hom.:

33665

Cov.:

AF XY:

0.623

AC XY:

46239

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.209

AC:

8672

AN:

41476

American (AMR)

AF:

0.740

AC:

11296

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.707

AC:

2449

AN:

3462

East Asian (EAS)

AF:

0.954

AC:

4920

AN:

5158

South Asian (SAS)

AF:

0.774

AC:

3737

AN:

4826

European-Finnish (FIN)

AF:

0.801

AC:

8450

AN:

10550

Middle Eastern (MID)

AF:

0.673

AC:

198

AN:

294

European-Non Finnish (NFE)

AF:

0.759

AC:

51441

AN:

67804

Other (OTH)

AF:

0.639

AC:

1347

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1362

2724

4086

5448

6810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.718

Hom.:

191802

Bravo

AF:

0.596

TwinsUK

AF:

0.766

AC:

2839

ALSPAC

AF:

0.768

AC:

2960

ESP6500AA

AF:

0.213

AC:

939

ESP6500EA

AF:

0.761

AC:

6546

ExAC

AF:

0.737

AC:

89422

Asia WGS

AF:

0.821

AC:

2850

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.021

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.032

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0000013

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

PhyloP100

-1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.50

REVEL

Benign

0.028

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.023

MPC

0.44

ClinPred

0.00066

GERP RS

-2.9

Varity_R

0.026

gMVP

0.18

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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