rs61733329

Variant names:

• chr7-151017080-C-T
• rs61733329
• NM_001317056.2:c.2245G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001317056.2(ATG9B):​c.2245G>A​(p.Gly749Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,607,570 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 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: 𝑓 0.0042 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (97 hom.)
• Consequence: ATG9B NM_001317056.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609
• Publications: 6 publications found

Genes affected

ATG9B (HGNC:21899): (autophagy related 9B) This gene functions in the regulation of autophagy, a lysosomal degradation pathway. This gene also functions as an antisense transcript in the posttranscriptional regulation of the endothelial nitric oxide synthase 3 gene, which has 3' overlap with this gene on the opposite strand. Mutations in this gene and disruption of the autophagy process have been associated with multiple cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0026526153).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317056.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG9B	NM_001317056.2	MANE Select	c.2245G>A	p.Gly749Ser	missense	Exon 9 of 14	NP_001303985.1
	ATG9B	NR_073169.1		n.1173G>A		non_coding_transcript_exon	Exon 9 of 18
	ATG9B	NR_133652.1		n.2321G>A		non_coding_transcript_exon	Exon 9 of 17

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATG9B	ENST00000639579.2	TSL:1 MANE Select	c.2245G>A	p.Gly749Ser	missense	Exon 9 of 14	ENSP00000491504.1
	ATG9B	ENST00000605952.5	TSL:1	n.2245G>A		non_coding_transcript_exon	Exon 9 of 17	ENSP00000475737.2
	ATG9B	ENST00000617967.4	TSL:1	n.1139G>A		non_coding_transcript_exon	Exon 9 of 18

Frequencies

GnomAD3 genomes AF: 0.00420 AC: 639 AN: 151990 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.0689

Gnomad SAS AF: 0.00499

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00624 AC: 1468 AN: 235102 AF XY: 0.00588

Gnomad AFR exome AF: 0.00403

Gnomad AMR exome AF: 0.000209

Gnomad ASJ exome AF: 0.00744

Gnomad EAS exome AF: 0.0686

Gnomad FIN exome AF: 0.000201

Gnomad NFE exome AF: 0.000303

Gnomad OTH exome AF: 0.00437

GnomAD4 exome AF: 0.00218 AC: 3172 AN: 1455462 Hom.: 97 Cov.: 33 AF XY: 0.00219 AC XY: 1584 AN XY: 723628

African (AFR) AF: 0.00338 AC: 113 AN: 33388

American (AMR) AF: 0.000182 AC: 8 AN: 44042

Ashkenazi Jewish (ASJ) AF: 0.00646 AC: 168 AN: 25988

East Asian (EAS) AF: 0.0530 AC: 2088 AN: 39426

South Asian (SAS) AF: 0.00322 AC: 275 AN: 85306

European-Finnish (FIN) AF: 0.000501 AC: 26 AN: 51948

Middle Eastern (MID) AF: 0.000893 AC: 5 AN: 5600

European-Non Finnish (NFE) AF: 0.000133 AC: 148 AN: 1109716

Other (OTH) AF: 0.00568 AC: 341 AN: 60048

GnomAD4 genome AF: 0.00421 AC: 641 AN: 152108 Hom.: 20 Cov.: 32 AF XY: 0.00436 AC XY: 324 AN XY: 74338

African (AFR) AF: 0.00398 AC: 165 AN: 41482

American (AMR) AF: 0.00288 AC: 44 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00837 AC: 29 AN: 3466

East Asian (EAS) AF: 0.0686 AC: 354 AN: 5158

South Asian (SAS) AF: 0.00520 AC: 25 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67976

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00248 Hom.: 9

Bravo AF: 0.00446

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00254 AC: 10

ESP6500EA AF: 0.000363 AC: 3

ExAC AF: 0.00581 AC: 701

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.5
DANN	Benign	0.65
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.61
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.60	T
Polyphen		0.0010	B
Vest4		0.23
MVP		0.061
ClinPred		0.0050	T
GERP RS		-0.52
Varity_R		0.035
gMVP		0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs61733329; hg19: chr7-150714167;