20-38634737-C-T

Variant names:

• chr20-38634737-C-T
• rs2088962694
• NM_001164431.3:c.901C>T

Variant summary

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

The NM_001164431.3(ARHGAP40):​c.901C>T​(p.Leu301Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 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: ARHGAP40 NM_001164431.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• Publications: 0 publications found

Genes affected

ARHGAP40 (HGNC:16226): (Rho GTPase activating protein 40) Predicted to enable GTPase activator activity. Predicted to be involved in regulation of actin filament polymerization and regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [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_001164431.3. 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
	ARHGAP40	NM_001164431.3	MANE Select	c.901C>T	p.Leu301Phe	missense	Exon 6 of 15	NP_001157903.2	Q5TG30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP40	ENST00000373345.9	TSL:5 MANE Select	c.901C>T	p.Leu301Phe	missense	Exon 6 of 15	ENSP00000362442.5	Q5TG30
	ARHGAP40	ENST00000906550.1		c.676C>T	p.Leu226Phe	missense	Exon 4 of 13	ENSP00000576609.1
	ARHGAP40	ENST00000243967.8	TSL:5	c.562C>T	p.Leu188Phe	missense	Exon 4 of 14	ENSP00000243967.4	H7BXE0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.0
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.11
Sift	Benign	0.39	T
Sift4G	Benign	0.14	T
Vest4		0.45
MutPred		0.80		Loss of stability (P = 0.0451)
MVP		0.061
ClinPred		0.97	D
GERP RS		1.8
Varity_R		0.065
gMVP		0.43
Mutation Taster		=89/11	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: rs2088962694; hg19: chr20-37263380;