rs779895655

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002853.4(RAD1):​c.518C>T​(p.Thr173Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,613,992 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T173R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

RAD1
NM_002853.4 missense

Scores

5
7
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.27
Variant links:
Genes affected
RAD1 (HGNC:9806): (RAD1 checkpoint DNA exonuclease) This gene encodes a component of a heterotrimeric cell cycle checkpoint complex, known as the 9-1-1 complex, that is activated to stop cell cycle progression in response to DNA damage or incomplete DNA replication. The 9-1-1 complex is recruited by RAD17 to affected sites where it may attract specialized DNA polymerases and other DNA repair effectors. Alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jan 2009]
TTC23L (HGNC:26355): (tetratricopeptide repeat domain 23 like) Predicted to be located in cytoplasm; microtubule cytoskeleton; and midbody. [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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.814

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAD1NM_002853.4 linkc.518C>T p.Thr173Met missense_variant Exon 4 of 6 ENST00000382038.7 NP_002844.1 O60671-1A0A024R045
RAD1NR_026591.2 linkn.567C>T non_coding_transcript_exon_variant Exon 3 of 5
TTC23LNR_169875.1 linkn.974-6762G>A intron_variant Intron 7 of 15
TTC23LNR_169876.1 linkn.1048-6762G>A intron_variant Intron 7 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAD1ENST00000382038.7 linkc.518C>T p.Thr173Met missense_variant Exon 4 of 6 1 NM_002853.4 ENSP00000371469.2 O60671-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000636
AC:
16
AN:
251448
Hom.:
0
AF XY:
0.0000883
AC XY:
12
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000523
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000472
AC:
69
AN:
1461830
Hom.:
1
Cov.:
31
AF XY:
0.0000605
AC XY:
44
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000661
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
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
Bravo
AF:
0.00000378
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.11
T;T
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.86
.;D
M_CAP
Benign
0.057
D
MetaRNN
Pathogenic
0.81
D;D
MetaSVM
Benign
-0.82
T
MutationAssessor
Pathogenic
3.2
M;M
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-3.5
D;D
REVEL
Uncertain
0.37
Sift
Uncertain
0.012
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;D
Vest4
0.73
MutPred
0.77
Gain of phosphorylation at S174 (P = 0.1837);Gain of phosphorylation at S174 (P = 0.1837);
MVP
0.60
MPC
0.41
ClinPred
0.83
D
GERP RS
5.7
Varity_R
0.19
gMVP
0.62

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: rs779895655; hg19: chr5-34911707; COSMIC: COSV57715388; COSMIC: COSV57715388; API