6-47714093-T-C

Position:

• chr6-47714093-T-C

Variant summary

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

The NM_153838.5(ADGRF4):​c.848T>C​(p.Leu283Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRF4 NM_153838.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72

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]

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
ADGRF4	NM_153838.5	c.848T>C	p.Leu283Pro	missense_variant	6/10	ENST00000283303.3	NP_722580.3
ADGRF4	NM_001347855.2	c.848T>C	p.Leu283Pro	missense_variant	6/10		NP_001334784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRF4	ENST00000283303.3	c.848T>C	p.Leu283Pro	missense_variant	6/10	1	NM_153838.5	ENSP00000283303.2
ADGRF4	ENST00000371220.5	c.1019T>C	p.Leu340Pro	missense_variant	7/11	5		ENSP00000360264.1
ADGRF4	ENST00000327753.7	c.848T>C	p.Leu283Pro	missense_variant	6/10	2		ENSP00000328319.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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

Oct 13, 2023

The c.848T>C (p.L283P) 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 848, causing the leucine (L) at amino acid position 283 to be replaced by a proline (P). 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	0.39
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	.;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.67	T;.;T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.71	T
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-4.7	D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.027	D;T;T
Polyphen		1.0	.;D;D
Vest4		0.41
MutPred		0.64		.;Loss of stability (P = 0.017);Loss of stability (P = 0.017);
MVP		0.61
MPC		0.31
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.80
gMVP		0.78

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

Other links and lift over

dbSNP: rs1771938404; hg19: chr6-47681829;