4-56307694-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393381.1(CRACD):c.280A>G(p.Asn94Asp) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CRACD NM_001393381.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.793

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16082096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRACD	NM_001393381.1	c.280A>G	p.Asn94Asp	missense_variant	5/11	ENST00000682029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRACD	ENST00000682029.1	c.280A>G	p.Asn94Asp	missense_variant	5/11		NM_001393381.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.280A>G (p.N94D) alteration is located in exon 5 (coding exon 2) of the KIAA1211 gene. This alteration results from a A to G substitution at nucleotide position 280, causing the asparagine (N) at amino acid position 94 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	19
Dann	Uncertain	0.99
Eigen	Benign	0.0020
Eigen_PC	Benign	-0.0064
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.77	T;T;.;T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.87	N;N;N
PrimateAI	Benign	0.42	T
Polyphen		0.78	.;.;P;P;P
Vest4		0.26, 0.25, 0.29
MutPred		0.20		.;Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);Loss of sheet (P = 0.0142);.;
MVP		0.19
MPC		0.51
ClinPred		0.68	D
GERP RS		3.0
Varity_R		0.20
gMVP		0.041

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: chr4-57173860;