rs200858282

Variant names:

• chr2-219221200-C-G
• rs200858282
• NM_001077198.3:c.2248G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-219221200-C-G
• chr2-219221200-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001077198.3(ATG9A):​c.2248G>C​(p.Ala750Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000653 in 1,591,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: ATG9A NM_001077198.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.184
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04130447).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077198.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG9A	NM_001077198.3	MANE Select	c.2248G>C	p.Ala750Pro	missense	Exon 14 of 16	NP_001070666.1	Q7Z3C6-1
	ATG9A	NM_024085.5		c.2248G>C	p.Ala750Pro	missense	Exon 13 of 15	NP_076990.4
	ATG9A	NR_104255.2		n.2372G>C		non_coding_transcript_exon	Exon 14 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG9A	ENST00000361242.9	TSL:2 MANE Select	c.2248G>C	p.Ala750Pro	missense	Exon 14 of 16	ENSP00000355173.4	Q7Z3C6-1
	ATG9A	ENST00000396761.6	TSL:1	c.2248G>C	p.Ala750Pro	missense	Exon 13 of 15	ENSP00000379983.2	Q7Z3C6-1
	ATG9A	ENST00000409033.7	TSL:1	n.*602G>C		non_coding_transcript_exon	Exon 14 of 16	ENSP00000386482.3	Q7Z3C6-3

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152062 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000224 AC: 5 AN: 223514 AF XY: 0.0000164

Gnomad AFR exome AF: 0.0000684

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000394

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000681 AC: 98 AN: 1439620 Hom.: 0 Cov.: 35 AF XY: 0.0000727 AC XY: 52 AN XY: 714828

African (AFR) AF: 0.00 AC: 0 AN: 32610

American (AMR) AF: 0.00 AC: 0 AN: 41186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24358

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.00 AC: 0 AN: 83158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.0000799 AC: 88 AN: 1101508

Other (OTH) AF: 0.000169 AC: 10 AN: 59314

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152062 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74268

African (AFR) AF: 0.0000483 AC: 2 AN: 41394

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000554 Hom.: 0

Bravo AF: 0.0000453

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000249 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	8.0
DANN	Benign	0.70
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.18
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.19
Sift	Benign	0.24	T
Sift4G	Benign	0.28	T
Polyphen		0.17	B
Vest4		0.098
MVP		0.42
MPC		0.29
ClinPred		0.017	T
GERP RS		-5.5
Varity_R		0.037
gMVP		0.24
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs200858282; hg19: chr2-220085922; COSMIC: COSV54698262; COSMIC: COSV54698262;