chr20-1239354-TG-AA

Variant names:

• chr20-1239354-TG-AA
• NM_001384355.1:c.689_690delTGinsAA
• RAD21L1 p.Met230Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001384355.1(RAD21L1):​c.689_690delTGinsAA​(p.Met230Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M230V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAD21L1 NM_001384355.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.689_690delTGinsAA	p.Met230Lys	missense	N/A	NP_001371284.1	A0A804HJ87
	RAD21L1	NM_001136566.3		c.689_690delTGinsAA	p.Met230Lys	missense	N/A	NP_001130038.2	Q9H4I0-1
	RAD21L1	NM_001384356.1		c.326_327delTGinsAA	p.Met109Lys	missense	N/A	NP_001371285.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21L1	ENST00000683101.1	MANE Select	c.689_690delTGinsAA	p.Met230Lys	missense	N/A	ENSP00000507397.1	A0A804HJ87
	RAD21L1	ENST00000409241.5	TSL:1	c.689_690delTGinsAA	p.Met230Lys	missense	N/A	ENSP00000386414.1	Q9H4I0-1
	RAD21L1	ENST00000402452.5	TSL:5	c.689_690delTGinsAA	p.Met230Lys	missense	N/A	ENSP00000385925.1	Q9H4I0-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.33

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-1219998;