3-48447048-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_130384.3(ATRIP):c.203C>T(p.Ser68Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000625 in 1,567,308 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
ATRIP
NM_130384.3 missense
NM_130384.3 missense
Scores
7
9
3
Clinical Significance
Conservation
PhyloP100: 5.27
Genes affected
ATRIP (HGNC:33499): (ATR interacting protein) This gene encodes an essential component of the DNA damage checkpoint. The encoded protein binds to single-stranded DNA coated with replication protein A. The protein also interacts with the ataxia telangiectasia and Rad3 related protein kinase, resulting in its accumulation at intranuclear foci induced by DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37744176).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATRIP | NM_130384.3 | c.203C>T | p.Ser68Leu | missense_variant | 1/13 | ENST00000320211.10 | NP_569055.1 | |
ATRIP-TREX1 | NR_153405.1 | n.270C>T | non_coding_transcript_exon_variant | 1/15 | ||||
ATRIP | NM_032166.4 | c.203C>T | p.Ser68Leu | missense_variant | 1/12 | NP_115542.2 | ||
ATRIP | NM_001271022.2 | c.-218+249C>T | intron_variant | NP_001257951.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATRIP | ENST00000320211.10 | c.203C>T | p.Ser68Leu | missense_variant | 1/13 | 1 | NM_130384.3 | ENSP00000323099 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000355 AC: 54AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000980 AC: 20AN: 204134Hom.: 0 AF XY: 0.000123 AC XY: 14AN XY: 113654
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GnomAD4 exome AF: 0.0000311 AC: 44AN: 1414998Hom.: 0 Cov.: 31 AF XY: 0.0000298 AC XY: 21AN XY: 703710
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GnomAD4 genome AF: 0.000355 AC: 54AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32AN XY: 74482
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 19, 2023 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 68 of the ATRIP protein (p.Ser68Leu). This variant is present in population databases (rs551289572, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ATRIP-related conditions. ClinVar contains an entry for this variant (Variation ID: 2414411). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Loss of disorder (P = 0.0745);Loss of disorder (P = 0.0745);
MVP
MPC
0.87
ClinPred
D
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at