Variant 6-46854032-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001098518.2(ADGRF5):c.4001C>T(p.Ser1334Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000866 in 1,605,032 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

ADGRF5
NM_001098518.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

Variant links:

Genes affected

ADGRF5 (HGNC:19030): (adhesion G protein-coupled receptor F5) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and cell surface receptor signaling pathway. Predicted to act upstream of or within several processes, including glomerular filtration; pharyngeal arch artery morphogenesis; and surfactant homeostasis. Located in cell surface and cytoplasmic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ADGRF5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015075058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRF5	NM_001098518.2 linkuse as main transcript	c.4001C>T	p.Ser1334Phe	missense_variant	21/21	ENST00000283296.12	NP_001091988.1	Q8IZF2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRF5	ENST00000283296.12 linkuse as main transcript	c.4001C>T	p.Ser1334Phe	missense_variant	21/21	1	NM_001098518.2	ENSP00000283296.7		Q8IZF2-1
ADGRF5	ENST00000265417.7 linkuse as main transcript	c.4001C>T	p.Ser1334Phe	missense_variant	21/21	1		ENSP00000265417.6		Q8IZF2-1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000119

AC:

AN:

243668

Hom.:

AF XY:

0.0000909

AC XY:

AN XY:

131980

show subpopulations

Gnomad AFR exome

AF:

0.000832

Gnomad AMR exome

AF:

0.0000305

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000746

Gnomad SAS exome

AF:

0.0000339

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.0000688

AC:

100

AN:

1452752

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

722636

show subpopulations

Gnomad4 AFR exome

AF:

0.000458

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000358

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00110

GnomAD4 genome

AF:

0.000256

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.000287

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Dec 15, 2023

The c.4001C>T (p.S1334F) alteration is located in exon 21 (coding exon 20) of the ADGRF5 gene. This alteration results from a C to T substitution at nucleotide position 4001, causing the serine (S) at amino acid position 1334 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

-0.10

Eigen_PC

Benign

0.035

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.87

D;.

M_CAP

Benign

0.020

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-2.4

N;N

REVEL

Benign

0.024

Sift

Benign

0.061

T;T

Sift4G

Uncertain

0.028

D;D

Polyphen

0.11

B;B

Vest4

0.33

MVP

0.043

MPC

0.24

ClinPred

0.028

GERP RS

4.3

Varity_R

0.073

gMVP

0.77

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