NM_001025598.2:c.2804G>T

Variant names:

• chr1-161048217-C-A
• rs367826999
• NM_001025598.2:c.2804G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025598.2(ARHGAP30):​c.2804G>T​(p.Arg935Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R935H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP30 NM_001025598.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

Genes affected

ARHGAP30 (HGNC:27414): (Rho GTPase activating protein 30) Predicted to enable GTPase activator activity. Predicted to be involved in small GTPase mediated signal transduction. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22291616).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025598.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP30	NM_001025598.2	MANE Select	c.2804G>T	p.Arg935Leu	missense	Exon 12 of 12	NP_001020769.1	Q7Z6I6-1
	ARHGAP30	NM_001287600.2		c.2360G>T	p.Arg787Leu	missense	Exon 11 of 11	NP_001274529.1	Q7Z6I6-3
	ARHGAP30	NM_001287602.2		c.2273G>T	p.Arg758Leu	missense	Exon 8 of 8	NP_001274531.1	A0A0A0MRJ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP30	ENST00000368013.8	TSL:2 MANE Select	c.2804G>T	p.Arg935Leu	missense	Exon 12 of 12	ENSP00000356992.3	Q7Z6I6-1
	ARHGAP30	ENST00000368015.1	TSL:5	c.2273G>T	p.Arg758Leu	missense	Exon 8 of 8	ENSP00000356994.1	A0A0A0MRJ8
	ARHGAP30	ENST00000368016.7	TSL:5	c.2171G>T	p.Arg724Leu	missense	Exon 13 of 13	ENSP00000356995.3	A0A0A0MRJ9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.092
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.098
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.16	T
Polyphen		0.84	P
Vest4		0.43
MVP		0.25
MPC		0.19
ClinPred		0.77	D
GERP RS		2.6
Varity_R		0.29
gMVP		0.13
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs367826999; hg19: chr1-161018007;