15-52608747-T-C

Variant names:

• chr15-52608747-T-C
• rs771075977
• NM_001385016.1:c.2167A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385016.1(ATOSA):​c.2167A>G​(p.Ile723Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,298 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I723L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ATOSA NM_001385016.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13261804).

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.2167A>G	p.Ile723Val	missense	Exon 6 of 13	NP_001371945.1	Q32MH5-1
	ATOSA	NM_001286495.2		c.2188A>G	p.Ile730Val	missense	Exon 5 of 12	NP_001273424.1	Q32MH5-3
	ATOSA	NM_001385019.1		c.2188A>G	p.Ile730Val	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.2167A>G	p.Ile723Val	missense	Exon 6 of 13	ENSP00000484641.1	Q32MH5-1
	ATOSA	ENST00000261844.11	TSL:1	c.2167A>G	p.Ile723Val	missense	Exon 6 of 13	ENSP00000261844.7	Q32MH5-1
	ATOSA	ENST00000399202.8	TSL:1	c.1903A>G	p.Ile635Val	missense	Exon 5 of 11	ENSP00000382153.4	H0Y3Q9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457298 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724822

African (AFR) AF: 0.00 AC: 0 AN: 33092

American (AMR) AF: 0.00 AC: 0 AN: 43844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26016

East Asian (EAS) AF: 0.00 AC: 0 AN: 39558

South Asian (SAS) AF: 0.00 AC: 0 AN: 84984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110758

Other (OTH) AF: 0.00 AC: 0 AN: 60184

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0055	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.060
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.48	T
Polyphen		0.80	P
Vest4		0.055
MutPred		0.23		Gain of sheet (P = 0.0827)
MVP		0.22
MPC		0.079
ClinPred		0.53	D
GERP RS		2.7
Varity_R		0.038
gMVP		0.053
Mutation Taster		=95/5	polymorphism

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: rs771075977; hg19: chr15-52900944;