Variant 4-41990736-G-GCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_006345.4(SLC30A9):c.86_87dup(p.Cys30ProfsTer13) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,611,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC30A9
NM_006345.4 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 0.323

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 Likely_pathogenic. Variant got 8 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.95 CDS is truncated, and there are 3 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 4-41990736-G-GCC is Pathogenic according to our data. Variant chr4-41990736-G-GCC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1300169.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A9	NM_006345.4 linkuse as main transcript	c.86_87dup	p.Cys30ProfsTer13	frameshift_variant	1/18	ENST00000264451.12
SLC30A9	XM_047449525.1 linkuse as main transcript	c.86_87dup	p.Cys30ProfsTer13	frameshift_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC30A9	ENST00000264451.12 linkuse as main transcript	c.86_87dup	p.Cys30ProfsTer13	frameshift_variant	1/18	1	NM_006345.4	P1
SLC30A9	ENST00000510460.1 linkuse as main transcript	n.211_212dup		non_coding_transcript_exon_variant	1/4	2
SLC30A9	ENST00000513699.5 linkuse as main transcript	c.86_87dup	p.Cys30ProfsTer13	frameshift_variant, NMD_transcript_variant	1/19	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000964

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

GnomAD3 exomes

AF:

0.00000416

AC:

AN:

240252

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132094

show subpopulations

Gnomad AFR exome

AF:

0.0000687

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725670

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:

0.0000263

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0000964

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

Bravo

AF:

0.0000340

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	May 04, 2022	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Genome Medicine, Institute for Basic Research in Developmental Disabilities	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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