9-35106359-T-C

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

6
7
6

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]

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
ATOSBNM_025182.4 linkc.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
ATOSBENST00000322813.10 linkc.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:
1
AN:
152182
Hom.:
0
Cov.:
32
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:
1
AN:
1461892
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
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:
1
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
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
D
BayesDel_noAF
Pathogenic
0.34
CADD
Pathogenic
26
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
D
LIST_S2
Benign
0.82
T;.;.;.;.;.;T
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.65
D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.18
T
MutationAssessor
Uncertain
2.5
.;M;M;M;M;M;M
PrimateAI
Uncertain
0.58
T
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
D
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.

Other links and lift over

dbSNP: rs1277566015; hg19: chr9-35106356; API