1-161047762-A-C

Variant names:

• chr1-161047762-A-C
• rs773900067
• NM_001025598.2:c.3259T>G

Variant summary

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

The NM_001025598.2(ARHGAP30):​c.3259T>G​(p.Tyr1087Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Y1087H) 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: 2.98
• 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 2 ACMG points.

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

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.3259T>G	p.Tyr1087Asp	missense	Exon 12 of 12	NP_001020769.1	Q7Z6I6-1
	ARHGAP30	NM_001287600.2		c.2815T>G	p.Tyr939Asp	missense	Exon 11 of 11	NP_001274529.1	Q7Z6I6-3
	ARHGAP30	NM_001287602.2		c.2728T>G	p.Tyr910Asp	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.3259T>G	p.Tyr1087Asp	missense	Exon 12 of 12	ENSP00000356992.3	Q7Z6I6-1
	ARHGAP30	ENST00000368015.1	TSL:5	c.2728T>G	p.Tyr910Asp	missense	Exon 8 of 8	ENSP00000356994.1	A0A0A0MRJ8
	ARHGAP30	ENST00000368016.7	TSL:5	c.2626T>G	p.Tyr876Asp	missense	Exon 13 of 13	ENSP00000356995.3	A0A0A0MRJ9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.25		Loss of phosphorylation at Y1087 (P = 0.017)
MVP		0.85
MPC		0.26
ClinPred		0.84	D
GERP RS		4.2
Varity_R		0.38
gMVP		0.39
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs773900067; hg19: chr1-161017552;