16-282655-C-A

Variant names:

• chr16-282655-C-A
• rs138141299
• NM_001176.4:c.519C>A

Variant summary

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

The NM_001176.4(ARHGDIG):​c.519C>A​(p.Ser173Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,446,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ARHGDIG NM_001176.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.39
• Publications: 0 publications found

Genes affected

ARHGDIG (HGNC:680): (Rho GDP dissociation inhibitor gamma) The GDP-dissociation inhibitors (GDIs) play a primary role in modulating the activation of GTPases by inhibiting the exchange of GDP for GTP. See ARHGDIB (MIM 602843).[supplied by OMIM, Nov 2010]

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 (MetaRNN=0.026695132).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001176.4. 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
	ARHGDIG	NM_001176.4	MANE Select	c.519C>A	p.Ser173Arg	missense	Exon 6 of 6	NP_001167.2	Q99819

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGDIG	ENST00000219409.8	TSL:1 MANE Select	c.519C>A	p.Ser173Arg	missense	Exon 6 of 6	ENSP00000219409.3	Q99819
	ARHGDIG	ENST00000856700.1		c.561C>A	p.Ser187Arg	missense	Exon 6 of 6	ENSP00000526759.1
	ARHGDIG	ENST00000965841.1		c.420C>A	p.Ser140Arg	missense	Exon 6 of 6	ENSP00000635900.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000277 AC: 4 AN: 1446486 Hom.: 0 Cov.: 36 AF XY: 0.00000139 AC XY: 1 AN XY: 717792

African (AFR) AF: 0.0000900 AC: 3 AN: 33326

American (AMR) AF: 0.00 AC: 0 AN: 43750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25304

East Asian (EAS) AF: 0.00 AC: 0 AN: 39388

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 83992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104240

Other (OTH) AF: 0.00 AC: 0 AN: 59680

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.0020
DANN	Benign	0.57
DEOGEN2	Benign	0.099	T
Eigen	Benign	-2.5
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-6.4
PrimateAI	Benign	0.43	T
PROVEAN	Benign	3.3	N
REVEL	Benign	0.060
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.47		Gain of MoRF binding (P = 0.0542)
MVP		0.20
MPC		0.063
ClinPred		0.050	T
GERP RS		-7.9
Varity_R		0.026
gMVP		0.15
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs138141299; hg19: chr16-332655;