Genetic Variant ATOSB:p.Thr371Ala (chr9-35106359-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_025182.4(ATOSB):c.1111A>G(p.Thr371Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ATOSB
NM_025182.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.44

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 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
ATOSB	NM_025182.4 link	c.1111A>G	p.Thr371Ala	missense_variant	Exon 6 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.1111A>G	p.Thr371Ala	missense_variant	Exon 6 of 9	1	NM_025182.4	ENSP00000319897.5		Q7L5A3-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1111A>G (p.T371A) alteration is located in exon 6 (coding exon 4) of the FAM214B gene. This alteration results from a A to G substitution at nucleotide position 1111, causing the threonine (T) at amino acid position 371 to be replaced by an alanine (A). 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

0.23

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

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

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

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

M_CAP

Benign

0.016

MetaRNN

Uncertain

0.65

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

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.5

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

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-4.7

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

REVEL

Uncertain

0.52

Sift

Uncertain

0.018

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

Sift4G

Benign

0.079

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

Polyphen

1.0

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

Vest4

0.77

MutPred

0.41

.;Loss of glycosylation at T371 (P = 0.0716);Loss of glycosylation at T371 (P = 0.0716);Loss of glycosylation at T371 (P = 0.0716);Loss of glycosylation at T371 (P = 0.0716);Loss of glycosylation at T371 (P = 0.0716);Loss of glycosylation at T371 (P = 0.0716);

MVP

0.42

MPC

0.81

ClinPred

0.99

GERP RS

5.4

Varity_R

0.54

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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