Variant chr20-51604848-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000338821.6(ATP9A):c.2976C>T(p.Ile992=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,547,294 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 57 hom. )

Consequence

ATP9A
ENST00000338821.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.322

Variant links:

Genes affected

ATP9A (HGNC:13540): (ATPase phospholipid transporting 9A (putative)) Enables protease binding activity. Involved in negative regulation of exosomal secretion; regulation of endocytic recycling; and regulation of retrograde transport, endosome to Golgi. Located in several cellular components, including endosome membrane; perinuclear region of cytoplasm; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATP9A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 20-51604848-G-A is Benign according to our data. Variant chr20-51604848-G-A is described in ClinVar as [Benign]. Clinvar id is 770302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.322 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00369 (562/152316) while in subpopulation AMR AF= 0.0286 (438/15290). AF 95% confidence interval is 0.0264. There are 9 homozygotes in gnomad4. There are 306 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP9A	NM_006045.3 linkuse as main transcript	c.2976C>T	p.Ile992=	synonymous_variant	27/28	ENST00000338821.6	NP_006036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP9A	ENST00000338821.6 linkuse as main transcript	c.2976C>T	p.Ile992=	synonymous_variant	27/28	1	NM_006045.3	ENSP00000342481	P1	O75110-1
ATP9A	ENST00000311637.9 linkuse as main transcript	c.2568C>T	p.Ile856=	synonymous_variant	22/23	1		ENSP00000309086

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

561

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0286

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0123

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00744

AC:

1485

AN:

199712

Hom.:

AF XY:

0.00565

AC XY:

609

AN XY:

107788

show subpopulations

Gnomad AFR exome

AF:

0.000672

Gnomad AMR exome

AF:

0.0462

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0158

Gnomad SAS exome

AF:

0.000404

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000322

Gnomad OTH exome

AF:

0.00774

GnomAD4 exome

AF:

0.00161

AC:

2252

AN:

1394978

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

987

AN XY:

689792

show subpopulations

Gnomad4 AFR exome

AF:

0.000361

Gnomad4 AMR exome

AF:

0.0447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00902

Gnomad4 SAS exome

AF:

0.000454

Gnomad4 FIN exome

AF:

0.0000387

Gnomad4 NFE exome

AF:

0.0000734

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.00369

AC:

562

AN:

152316

Hom.:

Cov.:

AF XY:

0.00411

AC XY:

306

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.0286

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0122

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.000237

Hom.:

Bravo

AF:

0.00634

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 15, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.1

DANN

Benign

0.79

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

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