15-52605156-C-T

Variant names:

• chr15-52605156-C-T
• rs764442968
• NM_001385016.1:c.2437G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001385016.1(ATOSA):​c.2437G>A​(p.Gly813Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000687 in 1,456,362 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: ATOSA NM_001385016.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.03
• Publications: 0 publications found

Genes affected

ATOSA (HGNC:25609): (atos homolog A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385016.1. 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
	ATOSA	NM_001385016.1	MANE Select	c.2437G>A	p.Gly813Arg	missense	Exon 7 of 13	NP_001371945.1	Q32MH5-1
	ATOSA	NM_001286495.2		c.2458G>A	p.Gly820Arg	missense	Exon 6 of 12	NP_001273424.1	Q32MH5-3
	ATOSA	NM_001385019.1		c.2458G>A	p.Gly820Arg	missense	Exon 7 of 13	NP_001371948.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATOSA	ENST00000619572.5	TSL:1 MANE Select	c.2437G>A	p.Gly813Arg	missense	Exon 7 of 13	ENSP00000484641.1	Q32MH5-1
	ATOSA	ENST00000261844.11	TSL:1	c.2437G>A	p.Gly813Arg	missense	Exon 7 of 13	ENSP00000261844.7	Q32MH5-1
	ATOSA	ENST00000399202.8	TSL:1	c.2173G>A	p.Gly725Arg	missense	Exon 6 of 11	ENSP00000382153.4	H0Y3Q9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000123 AC: 3 AN: 244224 AF XY: 0.00000753

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000300

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000687 AC: 10 AN: 1456362 Hom.: 0 Cov.: 30 AF XY: 0.00000690 AC XY: 5 AN XY: 724650

African (AFR) AF: 0.00 AC: 0 AN: 33158

American (AMR) AF: 0.00 AC: 0 AN: 43092

Ashkenazi Jewish (ASJ) AF: 0.000307 AC: 8 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39242

South Asian (SAS) AF: 0.00 AC: 0 AN: 85074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110528

Other (OTH) AF: 0.0000166 AC: 1 AN: 60094

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000828 AC: 1

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	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.90	L
PhyloP100		7.0
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.26		Gain of glycosylation at T812 (P = 0.0545)
MVP		0.30
MPC		0.52
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.80
gMVP		0.69
Mutation Taster		=22/78	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs764442968; hg19: chr15-52897353;