15-52605156-C-T

Position:

• chr15-52605156-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATOSA	NM_001385016.1	c.2437G>A	p.Gly813Arg	missense_variant	7/13	ENST00000619572.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATOSA	ENST00000619572.5	c.2437G>A	p.Gly813Arg	missense_variant	7/13	1	NM_001385016.1	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000123 AC: 3 AN: 244224 Hom.: 0 AF XY: 0.00000753 AC XY: 1 AN XY: 132850

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000307

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2022

The c.2437G>A (p.G813R) alteration is located in exon 7 (coding exon 6) of the FAM214A gene. This alteration results from a G to A substitution at nucleotide position 2437, causing the glycine (G) at amino acid position 813 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.90	L;.;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-6.2	D;D;.;D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0010	D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;.
Polyphen		1.0	D;.;D;.
Vest4		0.71
MutPred		0.26		Gain of glycosylation at T812 (P = 0.0545);.;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs764442968; hg19: chr15-52897353;