CRNKL1 p.Gly475Arg

Variant names:

• chr20-20039731-C-G
• NM_001278628.2:c.1423G>C
• CRNKL1 p.Gly475Arg

Your query was ambiguous. Multiple possible variants found:

• chr20-20039731-C-G
• chr20-20039731-C-T
• chr20-20039729-TCC-ACG
• chr20-20039729-TCC-GCG
• chr20-20039729-TCC-CCG
• chr20-20039729-TCC-CCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001278628.2(CRNKL1):​c.1423G>C​(p.Gly475Arg) 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. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRNKL1 NM_001278628.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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).
• BP4: Computational evidence support a benign effect (MetaRNN=0.358343).

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.1423G>C	p.Gly475Arg	missense	Exon 11 of 14	NP_001265557.1	Q9BZJ0-2
	CRNKL1	NM_016652.6		c.1906G>C	p.Gly636Arg	missense	Exon 12 of 15	NP_057736.4
	CRNKL1	NM_001278625.2		c.1870G>C	p.Gly624Arg	missense	Exon 12 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.1423G>C	p.Gly475Arg	missense	Exon 11 of 14	ENSP00000440733.1	Q9BZJ0-2
	CRNKL1	ENST00000377340.6	TSL:1	c.1906G>C	p.Gly636Arg	missense	Exon 12 of 15	ENSP00000366557.2	Q9BZJ0-1
	CRNKL1	ENST00000377327.8	TSL:1	c.1870G>C	p.Gly624Arg	missense	Exon 12 of 15	ENSP00000366544.4	Q5JY65

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.4
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.060
Sift	Benign	0.14	T
Sift4G	Benign	0.27	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.32
gMVP		0.59
Mutation Taster		=55/45	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

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

Other links and lift over

hg19: chr20-20020375;