15-52593657-A-G

Variant names:

• chr15-52593657-A-G
• NM_001385016.1:c.2729T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001385016.1(ATOSA):​c.2729T>C​(p.Phe910Ser) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATOSA NM_001385016.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.95

Genes affected

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

ENSG00000260618 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATOSA	NM_001385016.1	c.2729T>C	p.Phe910Ser	missense_variant	Exon 10 of 13	ENST00000619572.5	NP_001371945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOSA	ENST00000619572.5	c.2729T>C	p.Phe910Ser	missense_variant	Exon 10 of 13	1	NM_001385016.1	ENSP00000484641.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2729T>C (p.F910S) alteration is located in exon 10 (coding exon 9) of the FAM214A gene. This alteration results from a T to C substitution at nucleotide position 2729, causing the phenylalanine (F) at amino acid position 910 to be replaced by a serine (S). 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	0.98
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.;T;.
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	.;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.91	D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.0	M;.;M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-7.0	D;D;.;D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.010	D;D;.;D
Sift4G	Pathogenic	0.0010	D;D;D;.
Polyphen		1.0	D;.;D;.
Vest4		0.87
MutPred		0.73		Gain of disorder (P = 0.0047);.;Gain of disorder (P = 0.0047);.;
MVP		0.23
MPC		0.64
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.77
gMVP		0.73

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-52885854;