20-1228538-A-G

Variant names:

• chr20-1228538-A-G
• rs1161340148
• NM_001384355.1:c.85A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_001384355.1(RAD21L1):​c.85A>G​(p.Lys29Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000387 in 1,550,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RAD21L1 NM_001384355.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.25
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852
• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384355.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21L1	NM_001384355.1	MANE Select	c.85A>G	p.Lys29Glu	missense	Exon 2 of 14	NP_001371284.1	A0A804HJ87
	RAD21L1	NM_001136566.3		c.85A>G	p.Lys29Glu	missense	Exon 2 of 14	NP_001130038.2	Q9H4I0-1
	RAD21L1	NM_001384356.1		c.-90+2398A>G		intron	N/A	NP_001371285.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21L1	ENST00000683101.1	MANE Select	c.85A>G	p.Lys29Glu	missense	Exon 2 of 14	ENSP00000507397.1	A0A804HJ87
	RAD21L1	ENST00000409241.5	TSL:1	c.85A>G	p.Lys29Glu	missense	Exon 2 of 14	ENSP00000386414.1	Q9H4I0-1
	RAD21L1	ENST00000402452.5	TSL:5	c.85A>G	p.Lys29Glu	missense	Exon 2 of 14	ENSP00000385925.1	Q9H4I0-2

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152248 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

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

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398186 Hom.: 0 Cov.: 29 AF XY: 0.00000145 AC XY: 1 AN XY: 689660

African (AFR) AF: 0.00 AC: 0 AN: 31534

American (AMR) AF: 0.00 AC: 0 AN: 35488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

East Asian (EAS) AF: 0.00 AC: 0 AN: 35652

South Asian (SAS) AF: 0.00 AC: 0 AN: 79082

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078294

Other (OTH) AF: 0.00 AC: 0 AN: 57970

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152248 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74384

African (AFR) AF: 0.000121 AC: 5 AN: 41476

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000340

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	-0.070	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		9.2
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-4.0	D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.83
MVP		0.38
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.95
gMVP		0.52
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs1161340148; hg19: chr20-1209182;