chr16-282070-C-G

Variant names:

• chr16-282070-C-G
• rs964452083
• NM_001176.4:c.299C>G

Variant summary

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

The NM_001176.4(ARHGDIG):​c.299C>G​(p.Ser100Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,650 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S100L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ARHGDIG NM_001176.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• 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]

ENSG00000286901 (HGNC:):

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_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.299C>G	p.Ser100Trp	missense	Exon 3 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.299C>G	p.Ser100Trp	missense	Exon 3 of 6	ENSP00000219409.3	Q99819
	ARHGDIG	ENST00000856700.1		c.341C>G	p.Ser114Trp	missense	Exon 3 of 6	ENSP00000526759.1
	ARHGDIG	ENST00000447871.5	TSL:5	c.299C>G	p.Ser100Trp	missense	Exon 3 of 6	ENSP00000404435.1	A2ID99

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460650 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 726640

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111950

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	0.18
Eigen_PC	Benign	-0.025
FATHMM_MKL	Benign	0.39	N
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.63		Gain of catalytic residue at L98 (P = 0.004)
MVP		0.57
MPC		0.40
ClinPred		0.96	D
GERP RS		3.0
Varity_R		0.13
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs964452083; hg19: chr16-332070;