Variant 20-1244070-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001384355.1(RAD21L1):c.1208A>G(p.Asn403Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,550,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

RAD21L1
NM_001384355.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.596

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]

RAD21L1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037786365).

BS2

High AC in GnomAd at 88 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD21L1	NM_001384355.1 linkuse as main transcript	c.1208A>G	p.Asn403Ser	missense_variant	11/14	ENST00000683101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD21L1	ENST00000683101.1 linkuse as main transcript	c.1208A>G	p.Asn403Ser	missense_variant	11/14		NM_001384355.1	A1
RAD21L1	ENST00000409241.5 linkuse as main transcript	c.1208A>G	p.Asn403Ser	missense_variant	11/14	1		P4	Q9H4I0-1
RAD21L1	ENST00000402452.5 linkuse as main transcript	c.1208A>G	p.Asn403Ser	missense_variant	11/14	5			Q9H4I0-2

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

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:

0.000478

GnomAD3 exomes

AF:

0.000167

AC:

AN:

155940

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

82624

show subpopulations

Gnomad AFR exome

AF:

0.00317

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:

0.000229

GnomAD4 exome

AF:

0.0000665

AC:

AN:

1398114

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

689558

show subpopulations

Gnomad4 AFR exome

AF:

0.00257

Gnomad4 AMR exome

AF:

0.0000280

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:

0.000190

GnomAD4 genome

AF:

0.000578

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00209

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:

0.000473

Alfa

AF:

0.000401

Hom.:

Bravo

AF:

0.000684

ExAC

AF:

0.000124

AC:

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

Jun 18, 2021

The c.1208A>G (p.N403S) alteration is located in exon 11 (coding exon 10) of the RAD21L1 gene. This alteration results from a A to G substitution at nucleotide position 1208, causing the asparagine (N) at amino acid position 403 to be replaced by a serine (S). 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

Benign

0.066

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

Cadd

Benign

2.8

Dann

Benign

0.17

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.30

N;N

REVEL

Benign

0.099

Sift

Benign

0.48

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0030

.;B

Vest4

0.051

MVP

0.040

ClinPred

0.021

GERP RS

-0.97

Varity_R

0.025

gMVP

0.048

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over