4-42001818-C-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.274+38C>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 1,444,750 control chromosomes in the GnomAD database, including 431,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (35590 hom., cov: 31)
  • Exomes 𝑓: 0.78 (395714 hom.)
• Consequence: SLC30A9 NM_006345.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.08

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=-0.9).
• BP6: Variant 4-42001818-C-G is Benign according to our data. Variant chr4-42001818-C-G is described in ClinVar as [Benign]. Clinvar id is 1333131.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.274+38C>G		intron_variant		ENST00000264451.12
SLC30A9	XM_047449525.1	c.274+38C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A9	ENST00000264451.12	c.274+38C>G		intron_variant		1	NM_006345.4	P1
SLC30A9	ENST00000513699.5	c.274+38C>G		intron_variant, NMD_transcript_variant		2
SLC30A9	ENST00000510460.1	n.399+38C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96807 AN: 151724 Hom.: 35581 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.823

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.658

GnomAD3 exomes AF: 0.771 AC: 157657 AN: 204508 Hom.: 62867 AF XY: 0.777 AC XY: 86874 AN XY: 111738

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.832

Gnomad ASJ exome AF: 0.715

Gnomad EAS exome AF: 0.970

Gnomad SAS exome AF: 0.801

Gnomad FIN exome AF: 0.821

Gnomad NFE exome AF: 0.779

Gnomad OTH exome AF: 0.772

GnomAD4 exome AF: 0.777 AC: 1004152 AN: 1292908 Hom.: 395714 Cov.: 17 AF XY: 0.777 AC XY: 504699 AN XY: 649334

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.820

Gnomad4 ASJ exome AF: 0.715

Gnomad4 EAS exome AF: 0.968

Gnomad4 SAS exome AF: 0.802

Gnomad4 FIN exome AF: 0.816

Gnomad4 NFE exome AF: 0.783

Gnomad4 OTH exome AF: 0.749

GnomAD4 genome AF: 0.638 AC: 96836 AN: 151842 Hom.: 35590 Cov.: 31 AF XY: 0.646 AC XY: 47974 AN XY: 74268

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.798

Gnomad4 FIN AF: 0.823

Gnomad4 NFE AF: 0.777

Gnomad4 OTH AF: 0.662

Alfa AF: 0.703 Hom.: 7147

Bravo AF: 0.619

Asia WGS AF: 0.841 AC: 2920 AN: 3476

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	-0.90
Cadd	Benign	0.54
Dann	Benign	0.47

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: rs2581453; hg19: chr4-42003835;