chr1-3463380-C-T

Variant names:

• chr1-3463380-C-T
• rs1639453206
• NM_014448.4:c.296C>T

Variant summary

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

The NM_014448.4(ARHGEF16):​c.296C>T​(p.Ala99Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARHGEF16 NM_014448.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.67
• Publications: 0 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.296C>T	p.Ala99Val	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.296C>T	p.Ala99Val	missense	Exon 2 of 15	ENSP00000367629.4	Q5VV41-1
	ARHGEF16	ENST00000868563.1		c.296C>T	p.Ala99Val	missense	Exon 2 of 17	ENSP00000538622.1
	ARHGEF16	ENST00000868561.1		c.296C>T	p.Ala99Val	missense	Exon 2 of 15	ENSP00000538620.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.27
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		5.7
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.071
Sift	Benign	0.52	T
Sift4G	Benign	1.0	T
Polyphen		0.0060	B
Vest4		0.018
MutPred		0.18		Gain of methylation at K100 (P = 0.0416)
MVP		0.24
MPC		0.26
ClinPred		0.78	D
GERP RS		3.6
Varity_R		0.084
gMVP		0.19
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.39		Position offset: -2

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

Other links and lift over

dbSNP: rs1639453206; hg19: chr1-3379944;