X-24699490-C-A
Position:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001330360.2(POLA1):c.109C>A(p.Arg37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,177,537 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00033 ( 0 hom., 7 hem., cov: 22)
Exomes 𝑓: 0.000059 ( 0 hom. 13 hem. )
Consequence
POLA1
NM_001330360.2 missense
NM_001330360.2 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 1.44
Genes affected
POLA1 (HGNC:9173): (DNA polymerase alpha 1, catalytic subunit) This gene encodes the catalytic subunit of DNA polymerase, which together with a regulatory and two primase subunits, forms the DNA polymerase alpha complex. The catalytic subunit plays an essential role in the initiation of DNA replication. [provided by RefSeq, Mar 2010]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.021339446).
BP6
Variant X-24699490-C-A is Benign according to our data. Variant chrX-24699490-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1580975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000334 (37/110648) while in subpopulation AFR AF= 0.00112 (34/30400). AF 95% confidence interval is 0.000822. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 7 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POLA1 | NM_001330360.2 | c.109C>A | p.Arg37Ser | missense_variant | 2/37 | ENST00000379068.8 | NP_001317289.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POLA1 | ENST00000379068.8 | c.109C>A | p.Arg37Ser | missense_variant | 2/37 | 5 | NM_001330360.2 | ENSP00000368358 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 37AN: 110592Hom.: 0 Cov.: 22 AF XY: 0.000213 AC XY: 7AN XY: 32906
GnomAD3 genomes
AF:
AC:
37
AN:
110592
Hom.:
Cov.:
22
AF XY:
AC XY:
7
AN XY:
32906
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: 0.000141 AC: 22AN: 156056Hom.: 0 AF XY: 0.0000643 AC XY: 3AN XY: 46654
GnomAD3 exomes
AF:
AC:
22
AN:
156056
Hom.:
AF XY:
AC XY:
3
AN XY:
46654
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: 0.0000591 AC: 63AN: 1066889Hom.: 0 Cov.: 25 AF XY: 0.0000384 AC XY: 13AN XY: 338393
GnomAD4 exome
AF:
AC:
63
AN:
1066889
Hom.:
Cov.:
25
AF XY:
AC XY:
13
AN XY:
338393
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: 0.000334 AC: 37AN: 110648Hom.: 0 Cov.: 22 AF XY: 0.000212 AC XY: 7AN XY: 32972
GnomAD4 genome
AF:
AC:
37
AN:
110648
Hom.:
Cov.:
22
AF XY:
AC XY:
7
AN XY:
32972
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:
ESP6500AA
AF:
AC:
5
ESP6500EA
AF:
AC:
0
ExAC
AF:
AC:
22
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 08, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 08, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;.;D
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;M
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;D
REVEL
Benign
Sift
Uncertain
D;.;D
Sift4G
Uncertain
D;D;D
Polyphen
P;.;P
Vest4
MVP
MPC
0.43
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