1-3463380-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARHGEF16NM_014448.4 linkc.296C>T p.Ala99Val missense_variant Exon 2 of 15 ENST00000378378.9 NP_055263.2 Q5VV41-1B3KTS4
ARHGEF16XM_017001049.2 linkc.347C>T p.Ala116Val missense_variant Exon 2 of 15 XP_016856538.1
ARHGEF16XM_017001051.2 linkc.296C>T p.Ala99Val missense_variant Exon 2 of 15 XP_016856540.1 Q5VV41-1
ARHGEF16XM_047418009.1 linkc.347C>T p.Ala116Val missense_variant Exon 2 of 8 XP_047273965.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARHGEF16ENST00000378378.9 linkc.296C>T p.Ala99Val missense_variant Exon 2 of 15 2 NM_014448.4 ENSP00000367629.4 Q5VV41-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 08, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.296C>T (p.A99V) alteration is located in exon 2 (coding exon 1) of the ARHGEF16 gene. This alteration results from a C to T substitution at nucleotide position 296, causing the alanine (A) at amino acid position 99 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs1639453206; hg19: chr1-3379944; API