dbSNP rs1047626: SLC30A9:p.Met50Leu (chr4-42001654-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006345.4(SLC30A9):c.148A>C(p.Met50Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M50V) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC30A9
NM_006345.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

SLC30A9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042989463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A9	NM_006345.4 link	c.148A>C	p.Met50Leu	missense_variant	Exon 2 of 18	ENST00000264451.12	NP_006336.3	Q6PML9A0A0S2Z514
SLC30A9	XM_047449525.1 link	c.148A>C	p.Met50Leu	missense_variant	Exon 2 of 13		XP_047305481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC30A9	ENST00000264451.12 link	c.148A>C	p.Met50Leu	missense_variant	Exon 2 of 18	1	NM_006345.4	ENSP00000264451.6	Q6PML9
SLC30A9	ENST00000510460.1 link	n.273A>C		non_coding_transcript_exon_variant	Exon 2 of 4	2
SLC30A9	ENST00000513699.5 link	n.148A>C		non_coding_transcript_exon_variant	Exon 2 of 19	2		ENSP00000423529.1	D6R9M6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.91e-7

AC:

AN:

1446552

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719990

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32992

American (AMR)

AF:

0.00

AC:

AN:

42858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25852

East Asian (EAS)

AF:

0.00

AC:

AN:

39392

South Asian (SAS)

AF:

0.00

AC:

AN:

84310

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102260

Other (OTH)

AF:

0.00

AC:

AN:

59850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

191802

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.010

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.038

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.33

M_CAP

Benign

0.0061

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

PhyloP100

-1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.14

REVEL

Benign

0.0060

Sift

Benign

0.62

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.15

MutPred

0.18

Gain of catalytic residue at M50 (P = 0.0393);

MVP

0.030

MPC

0.40

ClinPred

0.028

GERP RS

-2.9

Varity_R

0.042

gMVP

0.17

Mutation Taster

=98/2

polymorphism

(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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over