18-79110412-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_198531.5(ATP9B):c.351A>C(p.Thr117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,611,524 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (23 hom.)
• Consequence: ATP9B NM_198531.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.67

Genes affected

ATP9B (HGNC:13541): (ATPase phospholipid transporting 9B (putative)) Predicted to enable ATPase-coupled intramembrane lipid transporter activity. Predicted to be involved in endocytosis; phospholipid translocation; and retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum. Located in perinuclear region of cytoplasm and trans-Golgi network. [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=-0.93).
• BP6: Variant 18-79110412-A-C is Benign according to our data. Variant chr18-79110412-A-C is described in ClinVar as [Benign]. Clinvar id is 710890.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.004 (5842/1459138) while in subpopulation AMR AF= 0.017 (755/44404). AF 95% confidence interval is 0.016. There are 23 homozygotes in gnomad4_exome. There are 2736 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP9B	NM_198531.5	c.351A>C	p.Thr117=	synonymous_variant	3/30	ENST00000426216.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP9B	ENST00000426216.6	c.351A>C	p.Thr117=	synonymous_variant	3/30	5	NM_198531.5	A1

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 572 AN: 152268 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00837

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00367

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00576 AC: 1437 AN: 249494 Hom.: 8 AF XY: 0.00508 AC XY: 686 AN XY: 134988

Gnomad AFR exome AF: 0.000682

Gnomad AMR exome AF: 0.0184

Gnomad ASJ exome AF: 0.000399

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000988

Gnomad FIN exome AF: 0.00959

Gnomad NFE exome AF: 0.00478

Gnomad OTH exome AF: 0.00760

GnomAD4 exome AF: 0.00400 AC: 5842 AN: 1459138 Hom.: 23 Cov.: 31 AF XY: 0.00377 AC XY: 2736 AN XY: 725904

Gnomad4 AFR exome AF: 0.000539

Gnomad4 AMR exome AF: 0.0170

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000698

Gnomad4 FIN exome AF: 0.00945

Gnomad4 NFE exome AF: 0.00390

Gnomad4 OTH exome AF: 0.00375

GnomAD4 genome AF: 0.00375 AC: 572 AN: 152386 Hom.: 1 Cov.: 33 AF XY: 0.00376 AC XY: 280 AN XY: 74524

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.0113

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00837

Gnomad4 NFE AF: 0.00367

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00257 Hom.: 2

Bravo AF: 0.00456

Asia WGS AF: 0.000578 AC: 2 AN: 3476

EpiCase AF: 0.00368

EpiControl AF: 0.00388

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.90
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs617472; hg19: chr18-76870412;