Variant 2-219221098-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001077198.3(ATG9A):c.2350C>T(p.Arg784Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,460,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ATG9A
NM_001077198.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.13

Variant links:

Genes affected

ATG9A (HGNC:22408): (autophagy related 9A) Acts upstream of or within autophagosome assembly. Located in endosome; phagophore assembly site; and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

ATG9A links:

ENSG00000284820 (HGNC:):

ENSG00000284820 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37150815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG9A	NM_001077198.3 link	c.2350C>T	p.Arg784Cys	missense_variant	14/16	ENST00000361242.9	NP_001070666.1	Q7Z3C6-1A0A024R438
ATG9A	NM_024085.5 link	c.2350C>T	p.Arg784Cys	missense_variant	13/15		NP_076990.4	Q7Z3C6-1A0A024R438
ATG9A	NR_104255.2 link	n.2474C>T		non_coding_transcript_exon_variant	14/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG9A	ENST00000361242.9 link	c.2350C>T	p.Arg784Cys	missense_variant	14/16	2	NM_001077198.3	ENSP00000355173.4		Q7Z3C6-1
ENSG00000284820	ENST00000446716.5 link	n.595C>T		non_coding_transcript_exon_variant	4/22	2		ENSP00000398528.1		H7C152

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000203

AC:

AN:

245708

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

133666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000659

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460786

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726594

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2024

The c.2350C>T (p.R784C) alteration is located in exon 14 (coding exon 12) of the ATG9A gene. This alteration results from a C to T substitution at nucleotide position 2350, causing the arginine (R) at amino acid position 784 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

T;T;T;.

Eigen

Benign

0.069

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

.;.;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.37

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.0

L;L;L;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.28

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

0.029

B;B;B;.

Vest4

0.58

MutPred

0.54

Loss of disorder (P = 0.036);Loss of disorder (P = 0.036);Loss of disorder (P = 0.036);.;

MVP

0.73

MPC

0.30

ClinPred

0.40

GERP RS

5.3

Varity_R

0.28

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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