4-152872517-A-G

Variant names:

• chr4-152872517-A-G
• NM_001025595.3:c.364A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025595.3(ARFIP1):​c.364A>G​(p.Met122Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M122T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARFIP1 NM_001025595.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67
• Publications: 0 publications found

Genes affected

ARFIP1 (HGNC:21496): (ADP ribosylation factor interacting protein 1) Enables phosphatidylinositol-4-phosphate binding activity. Involved in negative regulation of retrograde transport, endosome to Golgi. Acts upstream of or within intracellular protein transport and regulation of protein secretion. Located in Golgi membrane; cytosol; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12416774).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025595.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFIP1	NM_001025595.3	MANE Select	c.364A>G	p.Met122Val	missense	Exon 5 of 9	NP_001020766.1	B4E273
	ARFIP1	NM_001287431.2		c.364A>G	p.Met122Val	missense	Exon 5 of 9	NP_001274360.1	B4E273
	ARFIP1	NM_001287432.2		c.364A>G	p.Met122Val	missense	Exon 6 of 10	NP_001274361.1	P53367-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFIP1	ENST00000353617.7	TSL:5 MANE Select	c.364A>G	p.Met122Val	missense	Exon 5 of 9	ENSP00000296557.4	P53367-1
	ARFIP1	ENST00000451320.6	TSL:1	c.364A>G	p.Met122Val	missense	Exon 5 of 9	ENSP00000395083.2	P53367-1
	ARFIP1	ENST00000356064.3	TSL:1	c.268A>G	p.Met90Val	missense	Exon 4 of 8	ENSP00000348360.3	P53367-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.081
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.41	N
PhyloP100		4.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.19
Sift	Benign	0.39	T
Sift4G	Benign	0.59	T
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.28		Loss of ubiquitination at K124 (P = 0.1037)
MVP		0.79
MPC		0.28
ClinPred		0.57	D
GERP RS		6.0
Varity_R		0.13
gMVP		0.52
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

hg19: chr4-153793669;