chr20-1229925-G-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001384355.1(RAD21L1):c.190G>T(p.Val64Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000374 in 1,549,930 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
RAD21L1
NM_001384355.1 missense
NM_001384355.1 missense
Scores
11
5
3
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
RAD21L1 (HGNC:16271): (RAD21 cohesin complex component like 1) Predicted to enable chromatin binding activity. Predicted to be involved in mitotic sister chromatid cohesion; replication-born double-strand break repair via sister chromatid exchange; and synaptonemal complex assembly. Predicted to act upstream of or within several processes, including double-strand break repair via homologous recombination; homologous chromosome segregation; and seminiferous tubule development. Predicted to be located in lateral element. Predicted to be part of nuclear meiotic cohesin complex and nuclear mitotic cohesin complex. Predicted to be active in synaptonemal complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 35 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAD21L1 | NM_001384355.1 | c.190G>T | p.Val64Phe | missense_variant | 3/14 | ENST00000683101.1 | NP_001371284.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAD21L1 | ENST00000683101.1 | c.190G>T | p.Val64Phe | missense_variant | 3/14 | NM_001384355.1 | ENSP00000507397.1 | |||
RAD21L1 | ENST00000409241.5 | c.190G>T | p.Val64Phe | missense_variant | 3/14 | 1 | ENSP00000386414.1 | |||
RAD21L1 | ENST00000402452.5 | c.190G>T | p.Val64Phe | missense_variant | 3/14 | 5 | ENSP00000385925.1 | |||
RAD21L1 | ENST00000246108.3 | c.190G>T | p.Val64Phe | missense_variant | 3/3 | 3 | ENSP00000246108.3 |
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 152158Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000379 AC: 6AN: 158340Hom.: 0 AF XY: 0.0000240 AC XY: 2AN XY: 83478
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GnomAD4 exome AF: 0.0000165 AC: 23AN: 1397772Hom.: 0 Cov.: 29 AF XY: 0.0000116 AC XY: 8AN XY: 689426
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GnomAD4 genome AF: 0.000230 AC: 35AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74332
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 26, 2024 | The c.190G>T (p.V64F) alteration is located in exon 3 (coding exon 2) of the RAD21L1 gene. This alteration results from a G to T substitution at nucleotide position 190, causing the valine (V) at amino acid position 64 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0
.;D;.
Vest4
MVP
ClinPred
D
GERP RS
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gMVP
Splicing
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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