15-52587218-C-T

Position:

• chr15-52587218-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001385016.1(ATOSA):​c.2810G>A​(p.Gly937Asp) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATOSA NM_001385016.1 missense, splice_region
• Scores: Splicing: ADA: 0.9665
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.51

Genes affected

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

ENSG00000260618 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATOSA	NM_001385016.1	c.2810G>A	p.Gly937Asp	missense_variant, splice_region_variant	11/13	ENST00000619572.5	NP_001371945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATOSA	ENST00000619572.5	c.2810G>A	p.Gly937Asp	missense_variant, splice_region_variant	11/13	1	NM_001385016.1	ENSP00000484641.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Mar 18, 2024

The c.2810G>A (p.G937D) alteration is located in exon 11 (coding exon 10) of the FAM214A gene. This alteration results from a G to A substitution at nucleotide position 2810, causing the glycine (G) at amino acid position 937 to be replaced by an aspartic acid (D). 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	0.99
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;.;T;.
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;D;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.83	D;D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.6	M;.;M;.
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-5.7	D;D;.;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0020	D;D;.;D
Sift4G	Uncertain	0.0020	D;D;D;.
Polyphen		1.0	D;.;D;.
Vest4		0.89
MutPred		0.64		Loss of sheet (P = 0.0817);.;Loss of sheet (P = 0.0817);.;
MVP		0.39
MPC		0.52
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.92
gMVP		0.89

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.97
dbscSNV1_RF	Pathogenic	0.80
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

Publications

LitVar

Other links and lift over

dbSNP: rs1189211682; hg19: chr15-52879415;