rs562669866

Variant names:

• chr4-56313237-C-G
• rs562669866
• NM_001393381.1:c.395C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-56313237-C-G
• chr4-56313237-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_001393381.1(CRACD):​c.395C>G​(p.Ser132Cys) variant causes a missense change. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S132F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRACD NM_001393381.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.61
• Publications: 0 publications found

Genes affected

CRACD (HGNC:29219): (capping protein inhibiting regulator of actin dynamics) Involved in negative regulation of barbed-end actin filament capping. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity CRACD_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37858027).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393381.1. 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
	CRACD	NM_001393381.1	MANE Select	c.395C>G	p.Ser132Cys	missense	Exon 7 of 11	NP_001380310.1	Q6ZU35
	CRACD	NM_001393382.1		c.395C>G	p.Ser132Cys	missense	Exon 6 of 10	NP_001380311.1	Q6ZU35
	CRACD	NM_020722.2		c.395C>G	p.Ser132Cys	missense	Exon 7 of 11	NP_065773.1	Q6ZU35

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRACD	ENST00000682029.1	MANE Select	c.395C>G	p.Ser132Cys	missense	Exon 7 of 11	ENSP00000507165.1	Q6ZU35
	CRACD	ENST00000541073.5	TSL:1	c.374C>G	p.Ser125Cys	missense	Exon 6 of 10	ENSP00000444006.1	F5H1N7
	CRACD	ENST00000646253.2		c.650C>G	p.Ser217Cys	missense	Exon 8 of 12	ENSP00000495373.2	A0A2R8Y6P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.0062	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.6
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.32		Loss of disorder (P = 0.0112)
MVP		0.39
MPC		0.95
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.35
gMVP		0.29
Mutation Taster		=89/11	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

Other links and lift over

dbSNP: rs562669866; hg19: chr4-57179403;