17-81868514-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001301242.2(ARHGDIA):​c.865G>T​(p.Gly289Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 1,530,550 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 Benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00054 ( 0 hom. )

Consequence

ARHGDIA
NM_001301242.2 missense

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.78
Variant links:
Genes affected
ARHGDIA (HGNC:678): (Rho GDP dissociation inhibitor alpha) This gene encodes a protein that plays a key role in the regulation of signaling through Rho GTPases. The encoded protein inhibits the disassociation of Rho family members from GDP (guanine diphosphate), thereby maintaining these factors in an inactive state. Activity of this protein is important in a variety of cellular processes, and expression of this gene may be altered in tumors. Mutations in this gene have been found in individuals with nephrotic syndrome, type 8. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 17-81868514-C-A is Benign according to our data. Variant chr17-81868514-C-A is described in ClinVar as [Benign]. Clinvar id is 3338251.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARHGDIANM_004309.6 linkuse as main transcriptc.*362G>T 3_prime_UTR_variant 6/6 ENST00000269321.12 NP_004300.1 P52565-1V9HWE8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARHGDIAENST00000269321 linkuse as main transcriptc.*362G>T 3_prime_UTR_variant 6/61 NM_004309.6 ENSP00000269321.7 P52565-1

Frequencies

GnomAD3 genomes
AF:
0.000342
AC:
52
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000647
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000336
AC:
44
AN:
130958
Hom.:
0
AF XY:
0.000364
AC XY:
26
AN XY:
71412
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000228
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000586
Gnomad OTH exome
AF:
0.000500
GnomAD4 exome
AF:
0.000545
AC:
751
AN:
1378328
Hom.:
0
Cov.:
32
AF XY:
0.000527
AC XY:
358
AN XY:
679322
show subpopulations
Gnomad4 AFR exome
AF:
0.000159
Gnomad4 AMR exome
AF:
0.000368
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000279
Gnomad4 FIN exome
AF:
0.000240
Gnomad4 NFE exome
AF:
0.000634
Gnomad4 OTH exome
AF:
0.000364
GnomAD4 genome
AF:
0.000342
AC:
52
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.000282
AC XY:
21
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0000724
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000647
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000538
Hom.:
0
Bravo
AF:
0.000291

ClinVar

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

Submissions by phenotype

Nephrotic syndrome, type 8 Benign:1
Benign, criteria provided, single submitterclinical testingDr.Nikuei Genetic CenterJun 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
1.1
DANN
Benign
0.66

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs761416911; hg19: chr17-79826390; API