Variant chr1-3463476-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014448.4(ARHGEF16):c.392C>A(p.Ser131Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,375,314 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

ARHGEF16
NM_014448.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69

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]

ARHGEF16 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27427018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF16	NM_014448.4 linkuse as main transcript	c.392C>A	p.Ser131Tyr	missense_variant	2/15	ENST00000378378.9	NP_055263.2	Q5VV41-1B3KTS4
ARHGEF16	XM_017001049.2 linkuse as main transcript	c.443C>A	p.Ser148Tyr	missense_variant	2/15		XP_016856538.1
ARHGEF16	XM_017001051.2 linkuse as main transcript	c.392C>A	p.Ser131Tyr	missense_variant	2/15		XP_016856540.1	Q5VV41-1
ARHGEF16	XM_047418009.1 linkuse as main transcript	c.443C>A	p.Ser148Tyr	missense_variant	2/8		XP_047273965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGEF16	ENST00000378378.9 linkuse as main transcript	c.392C>A	p.Ser131Tyr	missense_variant	2/15	2	NM_014448.4	ENSP00000367629.4		Q5VV41-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000750

AC:

AN:

133274

Hom.:

AF XY:

0.00

AC XY:

AN XY:

71392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000200

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.27e-7

AC:

AN:

1375314

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

676522

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.37e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.392C>A (p.S131Y) alteration is located in exon 2 (coding exon 1) of the ARHGEF16 gene. This alteration results from a C to A substitution at nucleotide position 392, causing the serine (S) at amino acid position 131 to be replaced by a tyrosine (Y). 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

0.19

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

0.084

Eigen_PC

Benign

0.022

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.88

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.9

REVEL

Benign

0.12

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.015

Polyphen

0.82

Vest4

0.13

MutPred

0.25

Loss of glycosylation at S131 (P = 0.0757);

MVP

0.58

MPC

0.91

ClinPred

0.87

GERP RS

3.6

Varity_R

0.14

gMVP

0.48

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over