6-47713916-A-T

Position:

• chr6-47713916-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153838.5(ADGRF4):​c.671A>T​(p.Gln224Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRF4 NM_153838.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08166745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRF4	NM_153838.5	c.671A>T	p.Gln224Leu	missense_variant	6/10	ENST00000283303.3	NP_722580.3
ADGRF4	NM_001347855.2	c.671A>T	p.Gln224Leu	missense_variant	6/10		NP_001334784.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRF4	ENST00000283303.3	c.671A>T	p.Gln224Leu	missense_variant	6/10	1	NM_153838.5	ENSP00000283303.2
ADGRF4	ENST00000371220.5	c.842A>T	p.Gln281Leu	missense_variant	7/11	5		ENSP00000360264.1
ADGRF4	ENST00000327753.7	c.671A>T	p.Gln224Leu	missense_variant	6/10	2		ENSP00000328319.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

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

Feb 28, 2023

The c.671A>T (p.Q224L) alteration is located in exon 6 (coding exon 5) of the ADGRF4 gene. This alteration results from a A to T substitution at nucleotide position 671, causing the glutamine (Q) at amino acid position 224 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.0043	.;T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.64	T;.;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.082	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.040
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.35	.;B;B
Vest4		0.17
MutPred		0.35		.;Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);
MVP		0.27
MPC		0.044
ClinPred		0.18	T
GERP RS		4.3
Varity_R		0.099
gMVP		0.34

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: chr6-47681652;