rs2774279

Variant names:

• chr1-161047766-C-A
• rs2774279
• NM_001025598.2:c.3255G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-161047766-C-A
• chr1-161047766-C-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.3255G>T​(p.Arg1085Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 7.1e-7 (0 hom.)
• Consequence: ARHGAP30 NM_001025598.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732
• 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=0.070780426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP30	NM_001025598.2	c.3255G>T	p.Arg1085Ser	missense_variant	Exon 12 of 12	ENST00000368013.8	NP_001020769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP30	ENST00000368013.8	c.3255G>T	p.Arg1085Ser	missense_variant	Exon 12 of 12	2	NM_001025598.2	ENSP00000356992.3
ARHGAP30	ENST00000368015.1	c.2724G>T	p.Arg908Ser	missense_variant	Exon 8 of 8	5		ENSP00000356994.1
ARHGAP30	ENST00000368016.7	c.2622G>T	p.Arg874Ser	missense_variant	Exon 13 of 13	5		ENSP00000356995.3
ARHGAP30	ENST00000461003.5	n.4037G>T		non_coding_transcript_exon_variant	Exon 10 of 10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1413600 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 699960

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000317 AC: 1 AN: 31550

American (AMR) AF: 0.00 AC: 0 AN: 35772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22200

East Asian (EAS) AF: 0.00 AC: 0 AN: 39438

South Asian (SAS) AF: 0.00 AC: 0 AN: 77530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5490

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091738

Other (OTH) AF: 0.00 AC: 0 AN: 58254

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	4.6
DANN	Benign	0.67
DEOGEN2	Benign	0.019	.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	.;M;.
PhyloP100		-0.73
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.41	N;N;N
REVEL	Benign	0.091
Sift	Benign	0.13	T;D;T
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.61	.;P;.
Vest4		0.32
MutPred		0.11		.;Gain of phosphorylation at R1085 (P = 0.023);.;
MVP		0.26
MPC		0.10
ClinPred		0.18	T
GERP RS		-1.2
Varity_R		0.19
gMVP		0.24
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2774279; hg19: chr1-161017556;