chr15-52605164-G-A

Variant names:

• chr15-52605164-G-A
• rs2079278825
• NM_001385016.1:c.2429C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001385016.1(ATOSA):​c.2429C>T​(p.Pro810Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,457,760 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: 0.0000027 (0 hom.)
• Consequence: ATOSA NM_001385016.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.91

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 rank	MANE	Protein	UniProt
ATOSA	NM_001385016.1	c.2429C>T	p.Pro810Leu	missense_variant	Exon 7 of 13	ENST00000619572.5	NP_001371945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOSA	ENST00000619572.5	c.2429C>T	p.Pro810Leu	missense_variant	Exon 7 of 13	1	NM_001385016.1	ENSP00000484641.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1457760 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 725322

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000332

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

Dec 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2429C>T (p.P810L) alteration is located in exon 7 (coding exon 6) of the FAM214A gene. This alteration results from a C to T substitution at nucleotide position 2429, causing the proline (P) at amino acid position 810 to be replaced by a leucine (L). 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	Benign	0.24
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T;.;T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	.;D;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	0.90	L;.;L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.3	D;D;.;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;.
Polyphen		1.0	D;.;D;.
Vest4		0.53
MutPred		0.36		Loss of disorder (P = 0.0244);.;Loss of disorder (P = 0.0244);.;
MVP		0.14
MPC		0.49
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.48
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs2079278825; hg19: chr15-52897361;