NM_001077198.3:c.1988C>G

Variant names:

• chr2-219222311-G-C
• NM_001077198.3:c.1988C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077198.3(ATG9A):​c.1988C>G​(p.Ala663Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ATG9A NM_001077198.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037718564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG9A	NM_001077198.3	c.1988C>G	p.Ala663Gly	missense_variant	Exon 12 of 16	ENST00000361242.9	NP_001070666.1
ATG9A	NM_024085.5	c.1988C>G	p.Ala663Gly	missense_variant	Exon 11 of 15		NP_076990.4
ATG9A	NR_104255.2	n.2112C>G		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.1988C>G	p.Ala663Gly	missense_variant	Exon 12 of 16	2	NM_001077198.3	ENSP00000355173.4
ENSG00000284820	ENST00000446716.5	n.233C>G		non_coding_transcript_exon_variant	Exon 2 of 22	2		ENSP00000398528.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461038 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726832

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.26
DANN	Benign	0.64
DEOGEN2	Benign	0.038	T;T;T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.53	.;.;T;T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.038	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N;N;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.0	N;N;N;N;N
REVEL	Benign	0.028
Sift	Benign	0.47	T;T;T;T;T
Sift4G	Benign	0.47	T;T;T;T;.
Polyphen		0.0	B;B;B;.;.
Vest4		0.089
MutPred		0.21		Gain of catalytic residue at A663 (P = 0.0373);Gain of catalytic residue at A663 (P = 0.0373);Gain of catalytic residue at A663 (P = 0.0373);.;.;
MVP		0.26
MPC		0.22
ClinPred		0.025	T
GERP RS		-0.84
Varity_R		0.019
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-220087033;