20-1231594-C-A

Variant names:

• chr20-1231594-C-A
• NM_001384355.1:c.343C>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.343C>A​(p.His115Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,370,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RAD21L1 NM_001384355.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

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=0.2537828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD21L1	NM_001384355.1	c.343C>A	p.His115Asn	missense_variant	Exon 4 of 14	ENST00000683101.1	NP_001371284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD21L1	ENST00000683101.1	c.343C>A	p.His115Asn	missense_variant	Exon 4 of 14		NM_001384355.1	ENSP00000507397.1
RAD21L1	ENST00000409241.5	c.343C>A	p.His115Asn	missense_variant	Exon 4 of 14	1		ENSP00000386414.1
RAD21L1	ENST00000402452.5	c.343C>A	p.His115Asn	missense_variant	Exon 4 of 14	5		ENSP00000385925.1
RAD21L1	ENST00000477283.1	n.505C>A		non_coding_transcript_exon_variant	Exon 2 of 3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1370660 Hom.: 0 Cov.: 24 AF XY: 0.00000148 AC XY: 1 AN XY: 676778

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: 0.00000189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	.;T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.029
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.9	M;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-6.4	D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0080	D;D
Sift4G	Benign	0.075	T;D
Polyphen		0.061	.;B
Vest4		0.38
MutPred		0.31		Gain of disorder (P = 0.1119);Gain of disorder (P = 0.1119);
MVP		0.10
ClinPred		0.96	D
GERP RS		2.9
Varity_R		0.48
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-1212238;