rs1220210174

Variant names:

• chr20-1242729-A-C
• rs1220210174
• NM_001384355.1:c.967A>C

Your query was ambiguous. Multiple possible variants found:

• chr20-1242729-A-C
• chr20-1242729-A-G

Variant summary

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

The NM_001384355.1(RAD21L1):​c.967A>C​(p.Met323Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAD21L1 NM_001384355.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38

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=0.20260534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD21L1	NM_001384355.1	c.967A>C	p.Met323Leu	missense_variant	Exon 9 of 14	ENST00000683101.1	NP_001371284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD21L1	ENST00000683101.1	c.967A>C	p.Met323Leu	missense_variant	Exon 9 of 14		NM_001384355.1	ENSP00000507397.1
RAD21L1	ENST00000409241.5	c.967A>C	p.Met323Leu	missense_variant	Exon 9 of 14	1		ENSP00000386414.1
RAD21L1	ENST00000402452.5	c.967A>C	p.Met323Leu	missense_variant	Exon 9 of 14	5		ENSP00000385925.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	0.022
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.17
Sift	Benign	0.084	T;D
Sift4G	Uncertain	0.019	D;D
Polyphen		0.17	.;B
Vest4		0.28
MutPred		0.50		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.10
ClinPred		0.50	D
GERP RS		4.8
Varity_R		0.41
gMVP		0.040

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

Publications

LitVar

Other links and lift over

dbSNP: rs1220210174; hg19: chr20-1223373;