17-12928961-C-T

Variant summary

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

The NM_014859.6(ARHGAP44):c.497C>T(p.Ser166Phe) 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: ARHGAP44 NM_014859.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.88

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]

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=0.33999693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP44	NM_014859.6	c.497C>T	p.Ser166Phe	missense_variant	7/21	ENST00000379672.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP44	ENST00000379672.10	c.497C>T	p.Ser166Phe	missense_variant	7/21	1	NM_014859.6	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Oct 26, 2021

The c.497C>T (p.S166F) alteration is located in exon 7 (coding exon 7) of the ARHGAP44 gene. This alteration results from a C to T substitution at nucleotide position 497, causing the serine (S) at amino acid position 166 to be replaced by a phenylalanine (F). 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	0.26
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
Cadd	Pathogenic	28
Dann	Benign	0.97
DEOGEN2	Benign	0.30	T;.;T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	2.0	M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.2	D;D;.
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D;D;.
Sift4G	Uncertain	0.034	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.47
MutPred		0.55		Loss of phosphorylation at S166 (P = 0.0136);Loss of phosphorylation at S166 (P = 0.0136);Loss of phosphorylation at S166 (P = 0.0136);
MVP		0.12
MPC		1.7
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.44
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr17-12832278;