Variant 6-47009777-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_153840.4(ADGRF1):c.1658A>G(p.Asn553Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000082 ( 0 hom. )

Consequence

ADGRF1
NM_153840.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity AGRF1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.087741494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRF1	NM_153840.4 linkuse as main transcript	c.1658A>G	p.Asn553Ser	missense_variant	11/15	ENST00000371253.7	NP_722582.2
ADGRF1	XM_047418639.1 linkuse as main transcript	c.1070A>G	p.Asn357Ser	missense_variant	5/9		XP_047274595.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRF1	ENST00000371253.7 linkuse as main transcript	c.1658A>G	p.Asn553Ser	missense_variant	11/15	1	NM_153840.4	ENSP00000360299	P1	Q5T601-1
ADGRF1	ENST00000283297.5 linkuse as main transcript	c.1067A>G	p.Asn356Ser	missense_variant	5/9	1		ENSP00000283297
ADGRF1	ENST00000449332.6 linkuse as main transcript	n.1629A>G		non_coding_transcript_exon_variant	9/13	1
ADGRF1	ENST00000419892.6 linkuse as main transcript	n.7924A>G		non_coding_transcript_exon_variant	9/13	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727216

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 23, 2023

The c.1658A>G (p.N553S) alteration is located in exon 11 (coding exon 10) of the ADGRF1 gene. This alteration results from a A to G substitution at nucleotide position 1658, causing the asparagine (N) at amino acid position 553 to be replaced by a serine (S). 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

0.082

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.088

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.10

Sift

Benign

0.21

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.10

B;.

Vest4

0.15

MutPred

0.42

Loss of sheet (P = 0.1907);.;

MVP

0.32

MPC

0.068

ClinPred

0.26

GERP RS

4.7

Varity_R

0.051

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over