rs201948472
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_139076.3(ABRAXAS1):āc.125A>Gā(p.Lys42Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000298 in 1,612,592 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00026 ( 0 hom., cov: 33)
Exomes š: 0.00030 ( 0 hom. )
Consequence
ABRAXAS1
NM_139076.3 missense
NM_139076.3 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 3.85
Genes affected
ABRAXAS1 (HGNC:25829): (abraxas 1, BRCA1 A complex subunit) This gene encodes a protein that binds to the C-terminal repeats of breast cancer 1 (BRCA1) through a phospho-SXXF motif. The encoded protein recruits ubiquitin interaction motif containing 1 protein to BRCA1 protein and is required for DNA damage resistance, DNA repair, and cell cycle checkpoint control. Pseudogenes of this gene are found on chromosomes 3 and 8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03453189).
BP6
Variant 4-83482207-T-C is Benign according to our data. Variant chr4-83482207-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 128218.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABRAXAS1 | NM_139076.3 | c.125A>G | p.Lys42Arg | missense_variant | 2/9 | ENST00000321945.12 | NP_620775.2 | |
ABRAXAS1 | NM_001345962.2 | c.-136A>G | 5_prime_UTR_variant | 2/8 | NP_001332891.1 | |||
ABRAXAS1 | XR_001741334.3 | n.153A>G | non_coding_transcript_exon_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABRAXAS1 | ENST00000321945.12 | c.125A>G | p.Lys42Arg | missense_variant | 2/9 | 1 | NM_139076.3 | ENSP00000369857.3 |
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 152236Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
40
AN:
152236
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000303 AC: 75AN: 247884Hom.: 0 AF XY: 0.000253 AC XY: 34AN XY: 134584
GnomAD3 exomes
AF:
AC:
75
AN:
247884
Hom.:
AF XY:
AC XY:
34
AN XY:
134584
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000301 AC: 440AN: 1460356Hom.: 0 Cov.: 29 AF XY: 0.000299 AC XY: 217AN XY: 726526
GnomAD4 exome
AF:
AC:
440
AN:
1460356
Hom.:
Cov.:
29
AF XY:
AC XY:
217
AN XY:
726526
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000263 AC: 40AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.000323 AC XY: 24AN XY: 74378
GnomAD4 genome
AF:
AC:
40
AN:
152236
Hom.:
Cov.:
33
AF XY:
AC XY:
24
AN XY:
74378
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
27
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 15, 2016 | Variant summary: The FAM175A c.125A>G (p.Lys42Arg) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 28/122744 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0011211 (1/892). This frequency is about 12 times the estimated maximal expected allele frequency of a pathogenic FAM175A variant (0.0000313), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. This variant has been reported in one BrC pt without strong evidence for causality. In addition, one clinical diagnostic lab classified this variant as uncertain significance, without evidence to independently evaluate. Taken together, this variant is classified as likely benign unitl more evidence becomes available. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 23, 2014 | FAM175A has been only recently described in association with cancer predisposition and the risks are not well understood. This variant is denoted FAM175A c.125A>G at the cDNA level, p.Lys42Arg (K42R) at the protein level, and results in the change of a Lysine to an Arginine (AAG>AGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. FAM175A Lys42Arg was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. This variant is a conservative substitution of one positive polar amino acid for another, altering a position that is well conserved throughout evolution and is located in within the MPN-like domain. In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and the FAM175A gene, remain unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 06, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneKor MSA | Aug 01, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.
REVEL
Benign
Sift
Benign
T;.;.
Sift4G
Benign
T;T;T
Polyphen
D;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at