chr7-151017080-C-T

Position:

• chr7-151017080-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000639579.2(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. 10/14 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 ENST00000639579.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATG9B	NM_001317056.2	c.2245G>A	p.Gly749Ser	missense_variant	9/14	ENST00000639579.2	NP_001303985.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATG9B	ENST00000639579.2	c.2245G>A	p.Gly749Ser	missense_variant	9/14	1	NM_001317056.2	ENSP00000491504	P1
ATG9B	ENST00000617967.4	n.1139G>A		non_coding_transcript_exon_variant	9/18	1
ATG9B	ENST00000605952.5	c.2245G>A	p.Gly749Ser	missense_variant, NMD_transcript_variant	9/17	1		ENSP00000475737
ATG9B	ENST00000469530.4	c.2245G>A	p.Gly749Ser	missense_variant	9/13	5		ENSP00000479879	P1

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

GnomAD3 exomes AF: 0.00624 AC: 1468 AN: 235102 Hom.: 44 AF XY: 0.00588 AC XY: 757 AN XY: 128784

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 SAS exome AF: 0.00285

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

Gnomad4 AFR exome AF: 0.00338

Gnomad4 AMR exome AF: 0.000182

Gnomad4 ASJ exome AF: 0.00646

Gnomad4 EAS exome AF: 0.0530

Gnomad4 SAS exome AF: 0.00322

Gnomad4 FIN exome AF: 0.000501

Gnomad4 NFE exome AF: 0.000133

Gnomad4 OTH exome AF: 0.00568

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

Gnomad4 AFR AF: 0.00398

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.00837

Gnomad4 EAS AF: 0.0686

Gnomad4 SAS AF: 0.00520

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00134 Hom.: 0

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 v4.3

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;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;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.60	.;T
Polyphen		0.0010	B;B
Vest4		0.23
MVP		0.061
ClinPred		0.0050	T
GERP RS		-0.52
Varity_R		0.035
gMVP		0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs61733329; hg19: chr7-150714167;