Variant 4-41990684-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006345.4(SLC30A9):c.33C>G(p.His11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,610,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC30A9
NM_006345.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12058899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A9	NM_006345.4 linkuse as main transcript	c.33C>G	p.His11Gln	missense_variant	1/18	ENST00000264451.12
SLC30A9	XM_047449525.1 linkuse as main transcript	c.33C>G	p.His11Gln	missense_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC30A9	ENST00000264451.12 linkuse as main transcript	c.33C>G	p.His11Gln	missense_variant	1/18	1	NM_006345.4	P1
SLC30A9	ENST00000510460.1 linkuse as main transcript	n.158C>G		non_coding_transcript_exon_variant	1/4	2
SLC30A9	ENST00000513699.5 linkuse as main transcript	c.33C>G	p.His11Gln	missense_variant, NMD_transcript_variant	1/19	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457666

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724584

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

See cases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Apr 05, 2020

ACMG classification criteria: PM2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.048

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.38

M_CAP

Benign

0.025

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.50

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.65

REVEL

Benign

0.058

Sift

Uncertain

0.023

Sift4G

Uncertain

0.042

Polyphen

0.010

Vest4

0.43

MutPred

0.28

Gain of relative solvent accessibility (P = 0.0289);

MVP

0.040

MPC

0.78

ClinPred

0.19

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.087

gMVP

0.55

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

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