6-46858224-G-A

Position:

• chr6-46858224-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001098518.2(ADGRF5):​c.3679C>T​(p.Leu1227Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADGRF5 NM_001098518.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.827

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRF5	NM_001098518.2	c.3679C>T	p.Leu1227Phe	missense_variant	17/21	ENST00000283296.12	NP_001091988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRF5	ENST00000283296.12	c.3679C>T	p.Leu1227Phe	missense_variant	17/21	1	NM_001098518.2	ENSP00000283296.7
ADGRF5	ENST00000265417.7	c.3679C>T	p.Leu1227Phe	missense_variant	17/21	1		ENSP00000265417.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.3679C>T (p.L1227F) alteration is located in exon 17 (coding exon 16) of the ADGRF5 gene. This alteration results from a C to T substitution at nucleotide position 3679, causing the leucine (L) at amino acid position 1227 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	Uncertain	0.42
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.88	D;.
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Uncertain	0.33	D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Uncertain	0.49
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.18
MutPred		0.69		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.67
MPC		0.86
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.83
gMVP		0.72

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.

Other links and lift over

hg19: chr6-46825961;