NM_001077198.3:c.1864G>C

Variant names:

• chr2-219222435-C-G
• rs530808091
• NM_001077198.3:c.1864G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001077198.3(ATG9A):​c.1864G>C​(p.Ala622Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATG9A NM_001077198.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.79

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]

ENSG00000284820 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG9A	NM_001077198.3	c.1864G>C	p.Ala622Pro	missense_variant	Exon 12 of 16	ENST00000361242.9	NP_001070666.1
ATG9A	NM_024085.5	c.1864G>C	p.Ala622Pro	missense_variant	Exon 11 of 15		NP_076990.4
ATG9A	NR_104255.2	n.1988G>C		non_coding_transcript_exon_variant	Exon 12 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATG9A	ENST00000361242.9	c.1864G>C	p.Ala622Pro	missense_variant	Exon 12 of 16	2	NM_001077198.3	ENSP00000355173.4
ENSG00000284820	ENST00000446716.5	n.109G>C		non_coding_transcript_exon_variant	Exon 2 of 22	2		ENSP00000398528.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;T;.;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.87	.;.;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.63	D;D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.4	M;M;M;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.010	D;D;D;D;D
Sift4G	Uncertain	0.045	D;D;D;T;.
Polyphen		1.0	D;D;D;.;.
Vest4		0.86
MutPred		0.41		Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);.;.;
MVP		0.51
MPC		0.95
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.48
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs530808091; hg19: chr2-220087157;