rs530808091

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr2-219222435-C-A
• chr2-219222435-C-G
• chr2-219222435-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001077198.3(ATG9A):​c.1864G>T​(p.Ala622Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000706 in 1,416,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 7.1e-7 (0 hom.)
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4202127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATG9A	NM_001077198.3	c.1864G>T	p.Ala622Ser	missense_variant	Exon 12 of 16	ENST00000361242.9	NP_001070666.1
ATG9A	NM_024085.5	c.1864G>T	p.Ala622Ser	missense_variant	Exon 11 of 15		NP_076990.4
ATG9A	NR_104255.2	n.1988G>T		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>T	p.Ala622Ser	missense_variant	Exon 12 of 16	2	NM_001077198.3	ENSP00000355173.4
ENSG00000284820	ENST00000446716.5	n.109G>T		non_coding_transcript_exon_variant	Exon 2 of 22	2		ENSP00000398528.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416988 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 701132

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000266

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: 0.00

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	0.13
BayesDel_addAF	Benign	-0.0045	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T;T;T;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	.;.;D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.42	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;M;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.70	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.22	T;T;T;T;T
Sift4G	Benign	0.25	T;T;T;T;.
Polyphen		0.99	D;D;D;.;.
Vest4		0.61
MutPred		0.39		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);.;.;
MVP		0.32
MPC		0.75
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.082
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr2-220087157;