chr20-1229925-G-T

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

Scores

11
5
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0
Variant links:
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]

Genome browser will be placed here

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
RAD21L1NM_001384355.1 linkuse as main transcriptc.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
RAD21L1ENST00000683101.1 linkuse as main transcriptc.190G>T p.Val64Phe missense_variant 3/14 NM_001384355.1 ENSP00000507397.1 A0A804HJ87
RAD21L1ENST00000409241.5 linkuse as main transcriptc.190G>T p.Val64Phe missense_variant 3/141 ENSP00000386414.1 Q9H4I0-1
RAD21L1ENST00000402452.5 linkuse as main transcriptc.190G>T p.Val64Phe missense_variant 3/145 ENSP00000385925.1 Q9H4I0-2
RAD21L1ENST00000246108.3 linkuse as main transcriptc.190G>T p.Val64Phe missense_variant 3/33 ENSP00000246108.3 A0A140T8W2

Frequencies

GnomAD3 genomes
AF:
0.000230
AC:
35
AN:
152158
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000845
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000379
AC:
6
AN:
158340
Hom.:
0
AF XY:
0.0000240
AC XY:
2
AN XY:
83478
show subpopulations
Gnomad AFR exome
AF:
0.000727
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000165
AC:
23
AN:
1397772
Hom.:
0
Cov.:
29
AF XY:
0.0000116
AC XY:
8
AN XY:
689426
show subpopulations
Gnomad4 AFR exome
AF:
0.000665
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
AF:
0.000230
AC:
35
AN:
152158
Hom.:
0
Cov.:
33
AF XY:
0.000242
AC XY:
18
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.000845
Gnomad4 AMR
AF:
0.00
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
Alfa
AF:
0.000330
Hom.:
0
Bravo
AF:
0.000291
ESP6500AA
AF:
0.000723
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000396
AC:
1

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 submitterclinical testingAmbry GeneticsAug 26, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Benign
0.0069
T
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.48
.;T;.
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.97
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
1.0
D;D;D
M_CAP
Benign
0.038
D
MetaRNN
Uncertain
0.74
D;D;D
MetaSVM
Uncertain
-0.0059
T
MutationAssessor
Pathogenic
3.5
H;H;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-5.0
D;D;D
REVEL
Pathogenic
0.69
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.94
MVP
0.36
ClinPred
0.74
D
GERP RS
5.2
Varity_R
0.98
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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: rs377478024; hg19: chr20-1210569; API