20-1238166-G-A

Position:

• chr20-1238166-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001384355.1(RAD21L1):​c.598G>A​(p.Asp200Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000217 in 1,385,576 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: RAD21L1 NM_001384355.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17441347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD21L1	NM_001384355.1	c.598G>A	p.Asp200Asn	missense_variant	6/14	ENST00000683101.1	NP_001371284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD21L1	ENST00000683101.1	c.598G>A	p.Asp200Asn	missense_variant	6/14		NM_001384355.1	ENSP00000507397	A1
RAD21L1	ENST00000409241.5	c.598G>A	p.Asp200Asn	missense_variant	6/14	1		ENSP00000386414	P4
RAD21L1	ENST00000402452.5	c.598G>A	p.Asp200Asn	missense_variant	6/14	5		ENSP00000385925

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000217 AC: 3 AN: 1385576 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 683114

Gnomad4 AFR exome AF: 0.00

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: 0.00000280

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.598G>A (p.D200N) alteration is located in exon 6 (coding exon 5) of the RAD21L1 gene. This alteration results from a G to A substitution at nucleotide position 598, causing the aspartic acid (D) at amino acid position 200 to be replaced by an asparagine (N). 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	0.084
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T
Eigen	Benign	-0.094
Eigen_PC	Benign	0.0095
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	0.54	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	D;N
REVEL	Benign	0.15
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.0010	.;B
Vest4		0.14
MutPred		0.49		Loss of glycosylation at S201 (P = 0.0815);Loss of glycosylation at S201 (P = 0.0815);
MVP		0.15
ClinPred		0.73	D
GERP RS		4.3
Varity_R		0.064
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-1218810;