9-35105249-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025182.4(ATOSB):​c.1589A>T​(p.His530Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,613,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ATOSB
NM_025182.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.78
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.023447692).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATOSBNM_025182.4 linkc.1589A>T p.His530Leu 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
ATOSBENST00000322813.10 linkc.1589A>T p.His530Leu missense_variant Exon 9 of 9 1 NM_025182.4 ENSP00000319897.5 Q7L5A3-1

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000215
AC:
54
AN:
250972
Hom.:
0
AF XY:
0.000184
AC XY:
25
AN XY:
135658
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00148
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.0000438
AC:
64
AN:
1461510
Hom.:
0
Cov.:
31
AF XY:
0.0000426
AC XY:
31
AN XY:
727024
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00130
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:
0.0000828
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000851
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000901
Hom.:
0
Bravo
AF:
0.000140
ExAC
AF:
0.000148
AC:
18

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 26, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1589A>T (p.H530L) alteration is located in exon 9 (coding exon 7) of the FAM214B gene. This alteration results from a A to T substitution at nucleotide position 1589, causing the histidine (H) at amino acid position 530 to be replaced by a leucine (L). 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
0.083
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
23
DANN
Benign
0.97
DEOGEN2
Benign
0.0054
.;T;T;T;T;T;T
Eigen
Benign
-0.16
Eigen_PC
Benign
0.057
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.62
T;.;.;.;.;.;T
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.023
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.34
.;N;N;N;N;N;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.020
N;.;.;N;.;N;N
REVEL
Uncertain
0.40
Sift
Benign
0.24
T;.;.;T;.;T;T
Sift4G
Benign
0.38
T;T;T;T;T;T;T
Polyphen
0.14
.;B;B;B;B;B;B
Vest4
0.22
MutPred
0.18
.;Gain of stability (P = 0.0614);Gain of stability (P = 0.0614);Gain of stability (P = 0.0614);Gain of stability (P = 0.0614);Gain of stability (P = 0.0614);Gain of stability (P = 0.0614);
MVP
0.16
MPC
0.28
ClinPred
0.052
T
GERP RS
5.3
Varity_R
0.048
gMVP
0.40

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.

Other links and lift over

dbSNP: rs749379171; hg19: chr9-35105246; API