NM_001384355.1:c.731A>G

Variant names:

• chr20-1239396-A-G
• rs1046158401
• NM_001384355.1:c.731A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001384355.1(RAD21L1):​c.731A>G​(p.Asn244Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000974 in 1,540,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N244K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: RAD21L1 NM_001384355.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.357
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03340268).
• BP6: Variant 20-1239396-A-G is Benign according to our data. Variant chr20-1239396-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2596753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 14 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.731A>G	p.Asn244Ser	missense	Exon 7 of 14	NP_001371284.1	A0A804HJ87
	RAD21L1	NM_001136566.3		c.731A>G	p.Asn244Ser	missense	Exon 7 of 14	NP_001130038.2	Q9H4I0-1
	RAD21L1	NM_001384356.1		c.368A>G	p.Asn123Ser	missense	Exon 5 of 11	NP_001371285.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21L1	ENST00000683101.1	MANE Select	c.731A>G	p.Asn244Ser	missense	Exon 7 of 14	ENSP00000507397.1	A0A804HJ87
	RAD21L1	ENST00000409241.5	TSL:1	c.731A>G	p.Asn244Ser	missense	Exon 7 of 14	ENSP00000386414.1	Q9H4I0-1
	RAD21L1	ENST00000402452.5	TSL:5	c.731A>G	p.Asn244Ser	missense	Exon 7 of 14	ENSP00000385925.1	Q9H4I0-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000191 AC: 3 AN: 157302 AF XY: 0.0000120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000918

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000327

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000101 AC: 14 AN: 1388292 Hom.: 0 Cov.: 26 AF XY: 0.00000584 AC XY: 4 AN XY: 685498

African (AFR) AF: 0.00 AC: 0 AN: 31338

American (AMR) AF: 0.00 AC: 0 AN: 35582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25074

East Asian (EAS) AF: 0.0000842 AC: 3 AN: 35610

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.00000748 AC: 8 AN: 1069218

Other (OTH) AF: 0.0000347 AC: 2 AN: 57668

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.84
DANN	Benign	0.48
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.36
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.013
Sift	Benign	0.89	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.027
MutPred		0.40		Gain of glycosylation at N244 (P = 0.0075)
MVP		0.030
ClinPred		0.010	T
GERP RS		-2.8
Varity_R		0.028
gMVP		0.054
Mutation Taster		=97/3	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: rs1046158401; hg19: chr20-1220040;