chr1-3463547-C-G

Variant names:

• chr1-3463547-C-G
• rs1453195678
• NM_014448.4:c.463C>G

Variant summary

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

The NM_014448.4(ARHGEF16):​c.463C>G​(p.Arg155Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,309,442 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. R155W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ARHGEF16 NM_014448.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• Publications: 1 publications found

Genes affected

ARHGEF16 (HGNC:15515): (Rho guanine nucleotide exchange factor 16) Although the specific function of this protein is not known yet, it is thought to be involved in protein-protein and protein-lipid interactions. [provided by RefSeq, Jul 2008]

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_014448.4. 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
	ARHGEF16	NM_014448.4	MANE Select	c.463C>G	p.Arg155Gly	missense	Exon 2 of 15	NP_055263.2	Q5VV41-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGEF16	ENST00000378378.9	TSL:2 MANE Select	c.463C>G	p.Arg155Gly	missense	Exon 2 of 15	ENSP00000367629.4	Q5VV41-1
	ARHGEF16	ENST00000868563.1		c.463C>G	p.Arg155Gly	missense	Exon 2 of 17	ENSP00000538622.1
	ARHGEF16	ENST00000868561.1		c.463C>G	p.Arg155Gly	missense	Exon 2 of 15	ENSP00000538620.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1309442 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 635642

African (AFR) AF: 0.00 AC: 0 AN: 28650

American (AMR) AF: 0.00 AC: 0 AN: 22132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19392

East Asian (EAS) AF: 0.00 AC: 0 AN: 34926

South Asian (SAS) AF: 0.0000153 AC: 1 AN: 65148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5258

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1035190

Other (OTH) AF: 0.0000185 AC: 1 AN: 54038

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.26
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.019	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.34
MutPred		0.48		Gain of ubiquitination at K159 (P = 0.0199)
MVP		0.62
MPC		0.31
ClinPred		0.97	D
GERP RS		-2.0
Varity_R		0.21
gMVP		0.60
Mutation Taster		=50/50

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: rs1453195678; hg19: chr1-3380111;