4-56313356-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001393381.1(CRACD):c.514A>G(p.Lys172Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRACD NM_001393381.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.46

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29257166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRACD	NM_001393381.1	c.514A>G	p.Lys172Glu	missense_variant	7/11	ENST00000682029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRACD	ENST00000682029.1	c.514A>G	p.Lys172Glu	missense_variant	7/11		NM_001393381.1	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Apr 04, 2023

The c.514A>G (p.K172E) alteration is located in exon 7 (coding exon 4) of the KIAA1211 gene. This alteration results from a A to G substitution at nucleotide position 514, causing the lysine (K) at amino acid position 172 to be replaced by a glutamic acid (E). 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	Uncertain	0.55
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	22
Dann	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T;T;.;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.29	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Benign	0.35	T
Polyphen		0.93	.;.;P;P;P
Vest4		0.24, 0.23, 0.30
MutPred		0.17		.;Loss of methylation at K172 (P = 0.0443);Loss of methylation at K172 (P = 0.0443);Loss of methylation at K172 (P = 0.0443);.;
MVP		0.25
MPC		1.1
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.27
gMVP		0.15

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: chr4-57179522;