rs768590089

Variant names:

• chr15-22873575-T-A
• rs768590089
• NM_014608.6:c.3365A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-22873575-T-A
• chr15-22873575-T-C
• chr15-22873575-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014608.6(CYFIP1):​c.3365A>T​(p.Asp1122Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 7/11 in silico tools predict a damaging outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1122G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CYFIP1 NM_014608.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.97
• Publications: 0 publications found

Genes affected

CYFIP1 (HGNC:13759): (cytoplasmic FMR1 interacting protein 1) This gene encodes a protein that regulates cytoskeletal dynamics and protein translation. The encoded protein is a component of the WAVE regulatory complex (WRC), which promotes actin polymerization. This protein also interacts with the synaptic functional regulator FMR1 protein and translation initiation factor 4E to inhibit protein translation. A large chromosomal deletion including this gene is associated with increased risk of schizophrenia and epilepsy in human patients. Reduced expression of this gene has been observed in various human cancers and the encoded protein may inhibit tumor invasion. [provided by RefSeq, Mar 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.3365A>T	p.Asp1122Val	missense_variant	Exon 29 of 31	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.3365A>T	p.Asp1122Val	missense_variant	Exon 29 of 31	1	NM_014608.6	ENSP00000481038.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;.;T;T
LIST_S2	Pathogenic	1.0	.;D;D;D
MetaRNN	Pathogenic	0.92	D;D;D;D
PhyloP100		8.0
PROVEAN	Pathogenic	-8.6	.;.;.;D
Sift	Pathogenic	0.0	.;.;.;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Vest4		0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
gMVP		0.98

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: rs768590089; hg19: chr15-22999493;