NM_001025595.3:c.449G>C

Variant names:

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

Variant summary

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

The NM_001025595.3(ARFIP1):​c.449G>C​(p.Gly150Ala) variant causes a missense change involving the alteration of a 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: ARFIP1 NM_001025595.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>C	p.Gly150Ala	missense	Exon 6 of 9	NP_001020766.1	B4E273
	ARFIP1	NM_001287431.2		c.449G>C	p.Gly150Ala	missense	Exon 6 of 9	NP_001274360.1	B4E273
	ARFIP1	NM_001287432.2		c.449G>C	p.Gly150Ala	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>C	p.Gly150Ala	missense	Exon 6 of 9	ENSP00000296557.4	P53367-1
	ARFIP1	ENST00000451320.6	TSL:1	c.449G>C	p.Gly150Ala	missense	Exon 6 of 9	ENSP00000395083.2	P53367-1
	ARFIP1	ENST00000356064.3	TSL:1	c.353G>C	p.Gly118Ala	missense	Exon 5 of 8	ENSP00000348360.3	P53367-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.2	L
PhyloP100		10
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.41
Sift	Benign	0.12	T
Sift4G	Benign	0.20	T
Polyphen		0.66	P
Vest4		0.67
MutPred		0.37		Gain of glycosylation at S151 (P = 0.0151)
MVP		0.86
MPC		0.50
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.38
gMVP		0.56
Mutation Taster		=43/57	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;