NM_001278628.2:c.1723G>C

Variant names:

• chr20-20037496-C-G
• rs774304106
• NM_001278628.2:c.1723G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001278628.2(CRNKL1):​c.1723G>C​(p.Glu575Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRNKL1 NM_001278628.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.53

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRNKL1	NM_001278628.2	c.1723G>C	p.Glu575Gln	missense_variant	Exon 13 of 14	ENST00000536226.2	NP_001265557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRNKL1	ENST00000536226.2	c.1723G>C	p.Glu575Gln	missense_variant	Exon 13 of 14	1	NM_001278628.2	ENSP00000440733.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.058	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.038	.;B;.
Vest4		0.66
MutPred		0.34		.;Gain of MoRF binding (P = 0.0237);.;
MVP		0.70
MPC		0.28
ClinPred		0.88	D
GERP RS		5.0
Varity_R		0.46
gMVP		0.47

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

LitVar

Other links and lift over

dbSNP: rs774304106; hg19: chr20-20018140; COSMIC: COSV105121482; COSMIC: COSV105121482;