rs372153473

Variant names:

• chr15-52582231-C-A
• rs372153473
• NM_001385016.1:c.3154G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-52582231-C-A
• chr15-52582231-C-T

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.3154G>T​(p.Val1052Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000125 in 1,602,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ATOSA NM_001385016.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.74
• Publications: 0 publications found

Genes affected

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

ENSG00000260618 (HGNC:):

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=0.21217614).

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.3154G>T	p.Val1052Phe	missense	Exon 13 of 13	NP_001371945.1	Q32MH5-1
	ATOSA	NM_001286495.2		c.3175G>T	p.Val1059Phe	missense	Exon 12 of 12	NP_001273424.1	Q32MH5-3
	ATOSA	NM_001385019.1		c.3175G>T	p.Val1059Phe	missense	Exon 13 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.3154G>T	p.Val1052Phe	missense	Exon 13 of 13	ENSP00000484641.1	Q32MH5-1
	ATOSA	ENST00000261844.11	TSL:1	c.3154G>T	p.Val1052Phe	missense	Exon 13 of 13	ENSP00000261844.7	Q32MH5-1
	ATOSA	ENST00000568871.1	TSL:1	n.656G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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: 0.0000127 AC: 3 AN: 236766 AF XY: 0.00

Gnomad AFR exome AF: 0.000136

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: 0.00000911

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450758 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721556

African (AFR) AF: 0.0000306 AC: 1 AN: 32714

American (AMR) AF: 0.00 AC: 0 AN: 41906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 38920

South Asian (SAS) AF: 0.00 AC: 0 AN: 83782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108492

Other (OTH) AF: 0.00 AC: 0 AN: 59964

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74370

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000165 AC: 2

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	0.88
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.14
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.94	P
Vest4		0.39
MVP		0.068
MPC		0.55
ClinPred		0.59	D
GERP RS		4.7
Varity_R		0.43
gMVP		0.57

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: rs372153473; hg19: chr15-52874428;