20-63706410-G-C

Position:

• chr20-63706410-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000622789.5(ARFRP1):​c.211C>G​(p.Leu71Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARFRP1 ENST00000622789.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.17

Genes affected

ARFRP1 (HGNC:662): (ADP ribosylation factor related protein 1) The protein encoded by this gene is a membrane-associated GTP-ase which localizes to the plasma membrane and is related to the ADP-ribosylation factor (ARF) and ARF-like (ARL) proteins. This gene plays a role in membrane trafficking between the trans-Golgi network and endosomes. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, May 2012]

ARFRP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARFRP1	NM_001267547.3	c.211C>G	p.Leu71Val	missense_variant	4/8	ENST00000622789.5	NP_001254476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFRP1	ENST00000622789.5	c.211C>G	p.Leu71Val	missense_variant	4/8	1	NM_001267547.3	ENSP00000483486.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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, 2024

The c.211C>G (p.L71V) alteration is located in exon 4 (coding exon 3) of the ARFRP1 gene. This alteration results from a C to G substitution at nucleotide position 211, causing the leucine (L) at amino acid position 71 to be replaced by a valine (V). 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	0.23
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	.;D;.;D;D;.;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	.;.;D;D;.;D;D
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.025	D
MutationAssessor	Uncertain	2.4	.;M;M;M;M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.80	D
Sift4G	Uncertain	0.0060	D;D;T;D;D;D;D
Polyphen		1.0	.;D;.;D;D;.;.
Vest4		0.68
MutPred		0.67		.;Loss of stability (P = 0.2461);Loss of stability (P = 0.2461);Loss of stability (P = 0.2461);Loss of stability (P = 0.2461);Loss of stability (P = 0.2461);.;
MVP		0.80
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.76
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr20-62337762;