20-20040759-A-G

Variant names:

• chr20-20040759-A-G
• NM_001278628.2:c.1232T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001278628.2(CRNKL1):​c.1232T>C​(p.Phe411Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CRNKL1 NM_001278628.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.10

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.918

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRNKL1	NM_001278628.2	c.1232T>C	p.Phe411Ser	missense_variant	Exon 10 of 14	ENST00000536226.2	NP_001265557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRNKL1	ENST00000536226.2	c.1232T>C	p.Phe411Ser	missense_variant	Exon 10 of 14	1	NM_001278628.2	ENSP00000440733.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454498 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 723234

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.8	.;M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-7.5	D;D;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0090	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.86	.;P;.
Vest4		0.88
MutPred		0.80		.;Gain of disorder (P = 0.038);.;
MVP		0.66
MPC		1.3
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.87
gMVP		0.87

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: chr20-20021403;