17-45395523-A-G

Variant summary

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

The NM_001282290.2(ARHGAP27):c.2603T>C(p.Met868Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARHGAP27 NM_001282290.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.15

Genes affected

ARHGAP27 (HGNC:31813): (Rho GTPase activating protein 27) This gene encodes a member of a large family of proteins that activate Rho-type guanosine triphosphate (GTP) metabolizing enzymes. The encoded protein may pay a role in clathrin-mediated endocytosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP27	NM_001282290.2	c.2603T>C	p.Met868Thr	missense_variant	20/20	ENST00000685559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP27	ENST00000685559.1	c.2603T>C	p.Met868Thr	missense_variant	20/20		NM_001282290.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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 05, 2023

The c.1580T>C (p.M527T) alteration is located in exon 17 (coding exon 16) of the ARHGAP27 gene. This alteration results from a T to C substitution at nucleotide position 1580, causing the methionine (M) at amino acid position 527 to be replaced by a threonine (T). 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	0.70
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
Cadd	Pathogenic	27
Dann	Uncertain	0.98
DEOGEN2	Benign	0.052	T;T;.;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.50	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.5	N;D;N;D;N
REVEL	Benign	0.28
Sift	Benign	0.33	T;T;T;T;T
Sift4G	Benign	0.28	T;T;T;T;T
Polyphen		0.98	.;D;.;.;.
Vest4		0.70
MutPred		0.43		.;Gain of glycosylation at M868 (P = 0.036);.;.;.;
MVP		0.54
MPC		1.2
ClinPred		0.97	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.69

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: chr17-43472889;