rs200573018

Variant names:

• chr5-143134097-C-A
• NM_001135608.3:c.1829C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-143134097-C-A
• chr5-143134097-C-G
• chr5-143134097-C-T

Variant summary

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

The NM_001135608.3(ARHGAP26):​c.1829C>A​(p.Thr610Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARHGAP26 NM_001135608.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

Genes affected

ARHGAP26 (HGNC:17073): (Rho GTPase activating protein 26) Interaction of a cell with the extracellular matrix triggers integrin cell surface receptors to begin signaling cascades that regulate the organization of the actin-cytoskeleton. One of the proteins involved in these cascades is focal adhesion kinase. The protein encoded by this gene is a GTPase activating protein that binds to focal adhesion kinase and mediates the activity of the GTP binding proteins RhoA and Cdc42. Defects in this gene are a cause of juvenile myelomonocytic leukemia (JMML). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]

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=0.09086442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP26	NM_001135608.3	c.1829C>A	p.Thr610Lys	missense_variant	Exon 19 of 23	ENST00000645722.2	NP_001129080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP26	ENST00000645722.2	c.1829C>A	p.Thr610Lys	missense_variant	Exon 19 of 23		NM_001135608.3	ENSP00000495131.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457184 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 724700

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.80	.;T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.091	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;L;L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.75	N;.;N;.
REVEL	Benign	0.13
Sift	Benign	0.92	T;.;T;.
Sift4G	Benign	0.95	T;.;T;.
Polyphen		0.12	B;B;B;.
Vest4		0.27
MutPred		0.38		Gain of ubiquitination at T610 (P = 0.0066);Gain of ubiquitination at T610 (P = 0.0066);Gain of ubiquitination at T610 (P = 0.0066);.;
MVP		0.41
MPC		0.98
ClinPred		0.30	T
GERP RS		6.1
Varity_R		0.066
gMVP		0.43

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: chr5-142513662;