rs149499682

Variant names:

• chr15-52608607-A-C
• rs149499682
• NM_001385016.1:c.2307T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-52608607-A-C
• chr15-52608607-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001385016.1(ATOSA):​c.2307T>G​(p.Cys769Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000275 in 1,600,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: ATOSA NM_001385016.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.048257977).

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.2307T>G	p.Cys769Trp	missense	Exon 6 of 13	NP_001371945.1	Q32MH5-1
	ATOSA	NM_001286495.2		c.2328T>G	p.Cys776Trp	missense	Exon 5 of 12	NP_001273424.1	Q32MH5-3
	ATOSA	NM_001385019.1		c.2328T>G	p.Cys776Trp	missense	Exon 6 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.2307T>G	p.Cys769Trp	missense	Exon 6 of 13	ENSP00000484641.1	Q32MH5-1
	ATOSA	ENST00000261844.11	TSL:1	c.2307T>G	p.Cys769Trp	missense	Exon 6 of 13	ENSP00000261844.7	Q32MH5-1
	ATOSA	ENST00000399202.8	TSL:1	c.2043T>G	p.Cys681Trp	missense	Exon 5 of 11	ENSP00000382153.4	H0Y3Q9

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000253 AC: 6 AN: 236716 AF XY: 0.0000234

Gnomad AFR exome AF: 0.000328

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000914

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000193 AC: 28 AN: 1448298 Hom.: 0 Cov.: 31 AF XY: 0.0000194 AC XY: 14 AN XY: 720156

African (AFR) AF: 0.000493 AC: 16 AN: 32428

American (AMR) AF: 0.00 AC: 0 AN: 41084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25598

East Asian (EAS) AF: 0.00 AC: 0 AN: 39448

South Asian (SAS) AF: 0.0000361 AC: 3 AN: 83178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108116

Other (OTH) AF: 0.000151 AC: 9 AN: 59740

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74492

African (AFR) AF: 0.000385 AC: 16 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000489 Hom.: 0

Bravo AF: 0.000110

ESP6500AA AF: 0.000277 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000580 AC: 7

Asia WGS AF: 0.00145 AC: 5 AN: 3474

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	Benign	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0048	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.066
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.3
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.014	D
Polyphen		0.98	D
Vest4		0.45
MVP		0.13
MPC		0.38
ClinPred		0.43	T
GERP RS		4.7
Varity_R		0.43
gMVP		0.21
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149499682; hg19: chr15-52900804;