rs1200080538

Variant names:

• chr20-20038365-C-T
• rs1200080538
• NM_001278628.2:c.1631G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-20038365-C-T
• chr20-20038365-C-A
• chr20-20038365-C-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP2 BS2

The NM_001278628.2(CRNKL1):​c.1631G>A​(p.Arg544Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,398,322 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: CRNKL1 NM_001278628.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.71
• Publications: 1 publications found

Genes affected

CRNKL1 (HGNC:15762): (crooked neck pre-mRNA splicing factor 1) The crooked neck (crn) gene of Drosophila is essential for embryogenesis and is thought to be involved in cell cycle progression and pre-mRNA splicing. A protein encoded by this human locus has been found to localize to pre-mRNA splicing complexes in the nucleus and is necessary for pre-mRNA splicing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.87994 (below the threshold of 3.09). Trascript score misZ: 2.5211 (below the threshold of 3.09).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278628.2. 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
	CRNKL1	NM_001278628.2	MANE Select	c.1631G>A	p.Arg544Gln	missense	Exon 12 of 14	NP_001265557.1	Q9BZJ0-2
	CRNKL1	NM_016652.6		c.2114G>A	p.Arg705Gln	missense	Exon 13 of 15	NP_057736.4
	CRNKL1	NM_001278625.2		c.2078G>A	p.Arg693Gln	missense	Exon 13 of 15	NP_001265554.1	Q5JY65

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRNKL1	ENST00000536226.2	TSL:1 MANE Select	c.1631G>A	p.Arg544Gln	missense	Exon 12 of 14	ENSP00000440733.1	Q9BZJ0-2
	CRNKL1	ENST00000377340.6	TSL:1	c.2114G>A	p.Arg705Gln	missense	Exon 13 of 15	ENSP00000366557.2	Q9BZJ0-1
	CRNKL1	ENST00000377327.8	TSL:1	c.2078G>A	p.Arg693Gln	missense	Exon 13 of 15	ENSP00000366544.4	Q5JY65

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000127 AC: 2 AN: 157676 AF XY: 0.0000121

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000402

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000163

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1398322 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689882

African (AFR) AF: 0.00 AC: 0 AN: 31584

American (AMR) AF: 0.0000279 AC: 1 AN: 35808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25190

East Asian (EAS) AF: 0.00 AC: 0 AN: 35822

South Asian (SAS) AF: 0.00 AC: 0 AN: 79248

European-Finnish (FIN) AF: 0.0000203 AC: 1 AN: 49296

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

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1077724

Other (OTH) AF: 0.0000173 AC: 1 AN: 57956

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.086	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		7.7
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.59		Loss of MoRF binding (P = 0.0719)
MVP		0.64
MPC		0.91
ClinPred		0.99	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.48
gMVP		0.57
Mutation Taster		=10/90	disease causing

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: rs1200080538; hg19: chr20-20019009;