3-119365348-A-T

Variant names:

• chr3-119365348-A-T
• rs1483053797
• NM_020754.4:c.133A>T

Variant summary

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

The NM_020754.4(ARHGAP31):​c.133A>T​(p.Ile45Leu) variant causes a missense change involving the alteration of a 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. I45V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARHGAP31 NM_020754.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 0 publications found

Genes affected

ARHGAP31 (HGNC:29216): (Rho GTPase activating protein 31) This gene encodes a GTPase-activating protein (GAP). A variety of cellular processes are regulated by Rho GTPases which cycle between an inactive form bound to GDP and an active form bound to GTP. This cycling between inactive and active forms is regulated by guanine nucleotide exchange factors and GAPs. The encoded protein is a GAP shown to regulate two GTPases involved in protein trafficking and cell growth. [provided by RefSeq, Jul 2008]

ARHGAP31 Gene-Disease associations (from GenCC):

• Adams-Oliver syndrome 1

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Adams-Oliver syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP31	NM_020754.4	c.133A>T	p.Ile45Leu	missense_variant	Exon 2 of 12	ENST00000264245.9	NP_065805.2
ARHGAP31	XM_006713714.4	c.133A>T	p.Ile45Leu	missense_variant	Exon 2 of 12		XP_006713777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP31	ENST00000264245.9	c.133A>T	p.Ile45Leu	missense_variant	Exon 2 of 12	1	NM_020754.4	ENSP00000264245.4
ARHGAP31	ENST00000482743.1	c.46A>T	p.Ile16Leu	missense_variant	Exon 2 of 6	4		ENSP00000418429.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.
PhyloP100		9.3
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.021	D;T
Polyphen		0.71	P;.
Vest4		0.59
MutPred		0.62		Loss of helix (P = 0.3949);.;
MVP		0.40
MPC		1.3
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.52
gMVP		0.77
Mutation Taster		=54/46	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: rs1483053797; hg19: chr3-119084195;