17-12973309-A-G

Position:

• chr17-12973309-A-G

Variant summary

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

The ENST00000379672.10(ARHGAP44):​c.1531A>G​(p.Lys511Glu) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP44 ENST00000379672.10 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.77

Genes affected

ARHGAP44 (HGNC:29096): (Rho GTPase activating protein 44) Enables phospholipid binding activity. Predicted to be involved in several processes, including modification of dendritic spine; negative regulation of Rac protein signal transduction; and regulation of plasma membrane bounded cell projection organization. Located in leading edge membrane. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

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=0.4206521).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP44	NM_014859.6	c.1531A>G	p.Lys511Glu	missense_variant	17/21	ENST00000379672.10	NP_055674.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.1531A>G	p.Lys511Glu	missense_variant	17/21	1	NM_014859.6	ENSP00000368994	P4
	ENST00000623460.1	n.526T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Aug 16, 2022

The c.1531A>G (p.K511E) alteration is located in exon 17 (coding exon 17) of the ARHGAP44 gene. This alteration results from a A to G substitution at nucleotide position 1531, causing the lysine (K) at amino acid position 511 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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T;T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	0.84	D;D;D
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.4	N;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D;.;.
Sift4G	Benign	0.090	T;T;D
Polyphen		0.97	D;.;.
Vest4		0.52
MutPred		0.46		Loss of MoRF binding (P = 0.0103);Loss of MoRF binding (P = 0.0103);.;
MVP		0.28
MPC		1.5
ClinPred		0.90	D
GERP RS		5.3
Varity_R		0.22
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr17-12876626;