4-152881000-G-T

Variant names:

• chr4-152881000-G-T
• rs1467880651
• NM_001025595.3:c.449G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001025595.3(ARFIP1):​c.449G>T​(p.Gly150Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G150A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARFIP1 NM_001025595.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.783

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.449G>T	p.Gly150Val	missense	Exon 6 of 9	NP_001020766.1	B4E273
	ARFIP1	NM_001287431.2		c.449G>T	p.Gly150Val	missense	Exon 6 of 9	NP_001274360.1	B4E273
	ARFIP1	NM_001287432.2		c.449G>T	p.Gly150Val	missense	Exon 7 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.449G>T	p.Gly150Val	missense	Exon 6 of 9	ENSP00000296557.4	P53367-1
	ARFIP1	ENST00000451320.6	TSL:1	c.449G>T	p.Gly150Val	missense	Exon 6 of 9	ENSP00000395083.2	P53367-1
	ARFIP1	ENST00000356064.3	TSL:1	c.353G>T	p.Gly118Val	missense	Exon 5 of 8	ENSP00000348360.3	P53367-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250372 AF XY: 0.00

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	2.0	M
PhyloP100		10
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.59
Sift	Benign	0.070	T
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.75
MutPred		0.43		Gain of glycosylation at S151 (P = 0.0151)
MVP		0.93
MPC		0.91
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.78
gMVP		0.68
Mutation Taster		=34/66	disease causing

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

dbSNP: rs1467880651; hg19: chr4-153802152;