4-42022965-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006345.4(SLC30A9):c.527+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 1,254,614 control chromosomes in the GnomAD database, including 374,904 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (36033 hom., cov: 33)
  • Exomes 𝑓: 0.78 (338871 hom.)
• Consequence: SLC30A9 NM_006345.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.294

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-42022965-A-G is Benign according to our data. Variant chr4-42022965-A-G is described in ClinVar as [Benign]. Clinvar id is 1333134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A9	NM_006345.4	c.527+35A>G		intron_variant		ENST00000264451.12
SLC30A9	XM_047449525.1	c.527+35A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A9	ENST00000264451.12	c.527+35A>G		intron_variant		1	NM_006345.4	P1
SLC30A9	ENST00000513699.5	c.*284+35A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98392 AN: 152066 Hom.: 36021 Cov.: 33

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.670

GnomAD3 exomes AF: 0.766 AC: 155744 AN: 203252 Hom.: 61975 AF XY: 0.774 AC XY: 86426 AN XY: 111706

Gnomad AFR exome AF: 0.261

Gnomad AMR exome AF: 0.824

Gnomad ASJ exome AF: 0.714

Gnomad EAS exome AF: 0.970

Gnomad SAS exome AF: 0.799

Gnomad FIN exome AF: 0.823

Gnomad NFE exome AF: 0.780

Gnomad OTH exome AF: 0.781

GnomAD4 exome AF: 0.778 AC: 857852 AN: 1102430 Hom.: 338871 Cov.: 14 AF XY: 0.779 AC XY: 431063 AN XY: 553038

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.816

Gnomad4 ASJ exome AF: 0.715

Gnomad4 EAS exome AF: 0.969

Gnomad4 SAS exome AF: 0.803

Gnomad4 FIN exome AF: 0.817

Gnomad4 NFE exome AF: 0.783

Gnomad4 OTH exome AF: 0.753

GnomAD4 genome AF: 0.647 AC: 98435 AN: 152184 Hom.: 36033 Cov.: 33 AF XY: 0.655 AC XY: 48730 AN XY: 74392

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.673

Alfa AF: 0.693 Hom.: 8023

Bravo AF: 0.630

Asia WGS AF: 0.845 AC: 2929 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Psychomotor regression-oculomotor apraxia-movement disorder-nephropathy syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.2
Dann	Benign	0.51

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

Other links and lift over

dbSNP: rs13107768; hg19: chr4-42024982;