Genetic Variant NM_025182.4:c.1561G>A (chr9-35105277-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_025182.4(ATOSB):c.1561G>A(p.Glu521Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ATOSB
NM_025182.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.16

Variant links:

Genes affected

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

ATOSB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41573632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATOSB	NM_025182.4 link	c.1561G>A	p.Glu521Lys	missense_variant	Exon 9 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.1561G>A	p.Glu521Lys	missense_variant	Exon 9 of 9	1	NM_025182.4	ENSP00000319897.5		Q7L5A3-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000558

AC:

AN:

251090

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

203

AN:

1461772

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000172

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.0000340

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1561G>A (p.E521K) alteration is located in exon 9 (coding exon 7) of the FAM214B gene. This alteration results from a G to A substitution at nucleotide position 1561, causing the glutamic acid (E) at amino acid position 521 to be replaced by a lysine (K). 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

0.46

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

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

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

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

M_CAP

Benign

0.013

MetaRNN

Benign

0.42

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

MetaSVM

Benign

-0.53

MutationAssessor

Benign

2.0

.;M;M;M;M;M;M

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.9

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

REVEL

Uncertain

0.35

Sift

Uncertain

0.0030

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

Sift4G

Benign

0.095

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

Polyphen

1.0

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

Vest4

0.63

MVP

0.25

MPC

0.88

ClinPred

0.52

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.36

gMVP

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over