Variant 6-47009006-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000371253.7(ADGRF1):c.2429C>T(p.Thr810Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ADGRF1
ENST00000371253.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Variant links:

Genes affected

ADGRF1 (HGNC:18990): (adhesion G protein-coupled receptor F1) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within several processes, including memory; nervous system development; and positive regulation of CREB transcription factor activity. Predicted to be located in extracellular region and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ADGRF1 links:

ADGRF1 (HGNC:):

ADGRF1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14905703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRF1	NM_153840.4 linkuse as main transcript	c.2429C>T	p.Thr810Ile	missense_variant	11/15	ENST00000371253.7	NP_722582.2	Q5T601-1
ADGRF1	XM_047418639.1 linkuse as main transcript	c.1841C>T	p.Thr614Ile	missense_variant	5/9		XP_047274595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADGRF1	ENST00000371253.7 linkuse as main transcript	c.2429C>T	p.Thr810Ile	missense_variant	11/15	1	NM_153840.4	ENSP00000360299.2	Q5T601-1
ADGRF1	ENST00000283297.5 linkuse as main transcript	c.1838C>T	p.Thr613Ile	missense_variant	5/9	1		ENSP00000283297.5	A0A0C4DH10
ADGRF1	ENST00000449332.6 linkuse as main transcript	n.2400C>T		non_coding_transcript_exon_variant	9/13	1
ADGRF1	ENST00000419892.6 linkuse as main transcript	n.8695C>T		non_coding_transcript_exon_variant	9/13	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000598

AC:

AN:

250748

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135492

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:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461630

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727084

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:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000577

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

Feb 13, 2024

The c.2429C>T (p.T810I) alteration is located in exon 11 (coding exon 10) of the ADGRF1 gene. This alteration results from a C to T substitution at nucleotide position 2429, causing the threonine (T) at amino acid position 810 to be replaced by an isoleucine (I). 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

0.18

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

T;T

Eigen

Benign

-0.097

Eigen_PC

Benign

-0.022

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

0.97

D;D

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Benign

0.13

Sift

Uncertain

0.022

D;D

Sift4G

Benign

0.091

T;D

Polyphen

0.10

B;.

Vest4

0.32

MutPred

0.67

Gain of helix (P = 0.0696);.;

MVP

0.30

MPC

0.12

ClinPred

0.38

GERP RS

4.1

Varity_R

0.47

gMVP

0.47

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