20-38628947-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001164431.3(ARHGAP40):​c.579C>T​(p.Gly193Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000951 in 1,303,848 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

ARHGAP40
NM_001164431.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.81
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 20-38628947-C-T is Benign according to our data. Variant chr20-38628947-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652321.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.82 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGAP40NM_001164431.3 linkc.579C>T p.Gly193Gly synonymous_variant Exon 4 of 15 NP_001157903.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGAP40ENST00000373345.9 linkc.579C>T p.Gly193Gly synonymous_variant Exon 4 of 15 5 ENSP00000362442.5 Q5TG30
ARHGAP40ENST00000243967.8 linkc.240C>T p.Gly80Gly synonymous_variant Exon 2 of 14 5 ENSP00000243967.4 H7BXE0

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
151940
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00135
Gnomad SAS
AF:
0.00290
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000442
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000200
AC:
31
AN:
154852
Hom.:
0
AF XY:
0.000195
AC XY:
16
AN XY:
82102
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00102
Gnomad SAS exome
AF:
0.000797
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000167
Gnomad OTH exome
AF:
0.000231
GnomAD4 exome
AF:
0.0000851
AC:
98
AN:
1151790
Hom.:
0
Cov.:
31
AF XY:
0.000112
AC XY:
63
AN XY:
564800
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00102
Gnomad4 SAS exome
AF:
0.000815
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000652
Gnomad4 OTH exome
AF:
0.000409
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152058
Hom.:
1
Cov.:
32
AF XY:
0.000229
AC XY:
17
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00135
Gnomad4 SAS
AF:
0.00290
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.000474

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Sep 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ARHGAP40: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
0.78
DANN
Benign
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6070809; hg19: chr20-37257590; API