Genetic Variant ATOSB:p.Ser323Arg (chr9-35106628-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025182.4(ATOSB):c.969C>A(p.Ser323Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,401,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ATOSB
NM_025182.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.851

Variant links:

Genes affected

ATOSB (HGNC:25666): (atos homolog B) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ATOSB links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16322112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATOSB	NM_025182.4 link	c.969C>A	p.Ser323Arg	missense_variant	Exon 5 of 9	ENST00000322813.10	NP_079458.2	Q7L5A3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOSB	ENST00000322813.10 link	c.969C>A	p.Ser323Arg	missense_variant	Exon 5 of 9	1	NM_025182.4	ENSP00000319897.5		Q7L5A3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1401466

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

691512

show subpopulations

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:

0.00000278

Gnomad4 OTH exome

AF:

0.00

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 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.969C>A (p.S323R) alteration is located in exon 5 (coding exon 3) of the FAM214B gene. This alteration results from a C to A substitution at nucleotide position 969, causing the serine (S) at amino acid position 323 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

.;T;T;T;T;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.56

T;.;.;.;.;.;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.16

T;T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.6

.;L;L;L;L;L;L

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-2.2

N;.;.;N;.;N;N

REVEL

Benign

0.098

Sift

Uncertain

0.013

D;.;.;D;.;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

0.39

.;B;B;B;B;B;B

Vest4

0.33

MutPred

0.15

.;Loss of phosphorylation at S323 (P = 0.0036);Loss of phosphorylation at S323 (P = 0.0036);Loss of phosphorylation at S323 (P = 0.0036);Loss of phosphorylation at S323 (P = 0.0036);Loss of phosphorylation at S323 (P = 0.0036);Loss of phosphorylation at S323 (P = 0.0036);

MVP

0.13

MPC

0.29

ClinPred

0.46

GERP RS

2.1

Varity_R

0.20

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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