rs752441032

Variant names:

• chr2-219222341-C-G
• rs752441032
• NM_001077198.3:c.1958G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-219222341-C-G
• chr2-219222341-C-T

Variant summary

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

The NM_001077198.3(ATG9A):​c.1958G>C​(p.Arg653Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,046 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ATG9A NM_001077198.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.39

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.1958G>C	p.Arg653Pro	missense_variant	Exon 12 of 16	ENST00000361242.9	NP_001070666.1
ATG9A	NM_024085.5	c.1958G>C	p.Arg653Pro	missense_variant	Exon 11 of 15		NP_076990.4
ATG9A	NR_104255.2	n.2082G>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.1958G>C	p.Arg653Pro	missense_variant	Exon 12 of 16	2	NM_001077198.3	ENSP00000355173.4
ENSG00000284820	ENST00000446716.5	n.203G>C		non_coding_transcript_exon_variant	Exon 2 of 22	2		ENSP00000398528.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460836 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726704

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T;T;T;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	.;.;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.8	L;L;L;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.81	N;N;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.027	D;D;D;D;D
Sift4G	Benign	0.11	T;T;T;T;.
Polyphen		1.0	D;D;D;.;.
Vest4		0.72
MutPred		0.33		Gain of loop (P = 3e-04);Gain of loop (P = 3e-04);Gain of loop (P = 3e-04);.;.;
MVP		0.38
MPC		0.54
ClinPred		0.88	D
GERP RS		5.3
Varity_R		0.34
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs752441032; hg19: chr2-220087063;