Genetic Variant NM_001385016.1:c.2943G>A (chr15-52584879-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001385016.1(ATOSA):c.2943G>A(p.Met981Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ATOSA
NM_001385016.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

Variant links:

Genes affected

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

ATOSA links:

ENSG00000260618 (HGNC:):

ENSG00000260618 links:

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ACMG classification

Classification made for transcript

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 link	c.2943G>A	p.Met981Ile	missense_variant	Exon 12 of 13	ENST00000619572.5	NP_001371945.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOSA	ENST00000619572.5 link	c.2943G>A	p.Met981Ile	missense_variant	Exon 12 of 13	1	NM_001385016.1	ENSP00000484641.1		Q32MH5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2943G>A (p.M981I) alteration is located in exon 12 (coding exon 11) of the FAM214A gene. This alteration results from a G to A substitution at nucleotide position 2943, causing the methionine (M) at amino acid position 981 to be replaced by an isoleucine (I). 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

0.91

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

T;.;T;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

.;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.65

D;D;D;D

MetaSVM

Uncertain

-0.099

MutationAssessor

Pathogenic

3.4

M;.;M;.

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.8

D;D;.;D

REVEL

Uncertain

0.51

Sift

Uncertain

0.0010

D;D;.;D

Sift4G

Uncertain

0.0050

D;D;D;.

Polyphen

0.77

P;.;P;.

Vest4

0.80

MutPred

0.57

Loss of disorder (P = 0.2261);.;Loss of disorder (P = 0.2261);.;

MVP

0.37

MPC

0.30

ClinPred

1.0

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.67

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over