chr1-161047951-C-T

Variant names:

• chr1-161047951-C-T
• NM_001025598.2:c.3070G>A

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.3070G>A​(p.Gly1024Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP30 NM_001025598.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.556
• 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=0.11676249).

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.3070G>A	p.Gly1024Ser	missense	Exon 12 of 12	NP_001020769.1	Q7Z6I6-1
	ARHGAP30	NM_001287600.2		c.2626G>A	p.Gly876Ser	missense	Exon 11 of 11	NP_001274529.1	Q7Z6I6-3
	ARHGAP30	NM_001287602.2		c.2539G>A	p.Gly847Ser	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.3070G>A	p.Gly1024Ser	missense	Exon 12 of 12	ENSP00000356992.3	Q7Z6I6-1
	ARHGAP30	ENST00000368015.1	TSL:5	c.2539G>A	p.Gly847Ser	missense	Exon 8 of 8	ENSP00000356994.1	A0A0A0MRJ8
	ARHGAP30	ENST00000368016.7	TSL:5	c.2437G>A	p.Gly813Ser	missense	Exon 13 of 13	ENSP00000356995.3	A0A0A0MRJ9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.56
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.069
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.55	T
Polyphen		0.11	B
Vest4		0.11
MutPred		0.26		Gain of glycosylation at G1024 (P = 0.018)
MVP		0.37
MPC		0.034
ClinPred		0.60	D
GERP RS		3.9
Varity_R		0.17
gMVP		0.13
Mutation Taster		=83/17	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

hg19: chr1-161017741;