Variant 6-47714261-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000283303.3(ADGRF4):c.1016T>C(p.Ile339Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 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: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADGRF4
ENST00000283303.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.970

Variant links:

Genes affected

ADGRF4 (HGNC:19011): (adhesion G protein-coupled receptor F4) Sequence analysis of this gene suggests that it is encodes a member of the superfamily of G protein-couple receptors. G protein-coupled receptors typically contain seven hydrophobic transmembrane domains, interact with guanine nucleotide binding regulatory proteins, and detect molecules outside the cell and act to transduce these signals into intracellular responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2016]

ADGRF4 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=0.28589886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRF4	NM_153838.5 linkuse as main transcript	c.1016T>C	p.Ile339Thr	missense_variant	6/10	ENST00000283303.3	NP_722580.3
ADGRF4	NM_001347855.2 linkuse as main transcript	c.1016T>C	p.Ile339Thr	missense_variant	6/10		NP_001334784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADGRF4	ENST00000283303.3 linkuse as main transcript	c.1016T>C	p.Ile339Thr	missense_variant	6/10	1	NM_153838.5	ENSP00000283303	P1
ADGRF4	ENST00000371220.5 linkuse as main transcript	c.1187T>C	p.Ile396Thr	missense_variant	7/11	5		ENSP00000360264
ADGRF4	ENST00000327753.7 linkuse as main transcript	c.1016T>C	p.Ile339Thr	missense_variant	6/10	2		ENSP00000328319	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

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:

0.00000180

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

Oct 16, 2023

The c.1016T>C (p.I339T) alteration is located in exon 6 (coding exon 5) of the ADGRF4 gene. This alteration results from a T to C substitution at nucleotide position 1016, causing the isoleucine (I) at amino acid position 339 to be replaced by a threonine (T). 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

0.22

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

.;T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.69

T;.;T

M_CAP

Benign

0.0090

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

0.84

N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.074

T;T;T

Sift4G

Uncertain

0.018

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.13

MutPred

0.63

.;Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);

MVP

0.59

MPC

0.046

ClinPred

0.90

GERP RS

5.0

Varity_R

0.11

gMVP

0.24

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

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