ENST00000373345.9:c.83C>T

Variant names:

• chr20-38602025-C-T
• rs778330696
• NM_001164431.3:c.83C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000373345.9(ARHGAP40):​c.83C>T​(p.Pro28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000176 in 1,135,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: ARHGAP40 ENST00000373345.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.227
• 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]

ENSG00000289012 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000373345.9. 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.83C>T	p.Pro28Leu	missense	Exon 1 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.83C>T	p.Pro28Leu	missense	Exon 1 of 15	ENSP00000362442.5	Q5TG30
	ARHGAP40	ENST00000906550.1		c.83C>T	p.Pro28Leu	missense	Exon 1 of 13	ENSP00000576609.1
	ENSG00000289012	ENST00000688003.1		n.311+15864C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000765 AC: 1 AN: 130728 AF XY: 0.0000141

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000176 AC: 2 AN: 1135164 Hom.: 0 Cov.: 31 AF XY: 0.00000359 AC XY: 2 AN XY: 556732

African (AFR) AF: 0.00 AC: 0 AN: 24322

American (AMR) AF: 0.0000354 AC: 1 AN: 28222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15910

East Asian (EAS) AF: 0.00 AC: 0 AN: 12808

South Asian (SAS) AF: 0.0000132 AC: 1 AN: 76032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2806

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 920340

Other (OTH) AF: 0.00 AC: 0 AN: 41328

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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
BayesDel_noAF	Benign	-0.61
CADD	Benign	20
DANN	Benign	0.96
PhyloP100		0.23
PromoterAI		0.026	Neutral
Mutation Taster		=223/77	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: rs778330696; hg19: chr20-37230668;