chr4-152863610-T-G

Variant names:

• chr4-152863610-T-G
• rs1437956049
• NM_001025595.3:c.98T>G

Variant summary

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

The NM_001025595.3(ARFIP1):​c.98T>G​(p.Leu33Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000507 in 1,577,480 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ARFIP1 NM_001025595.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26
• 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.98T>G	p.Leu33Trp	missense	Exon 3 of 9	NP_001020766.1	B4E273
	ARFIP1	NM_001287431.2		c.98T>G	p.Leu33Trp	missense	Exon 3 of 9	NP_001274360.1	B4E273
	ARFIP1	NM_001287432.2		c.98T>G	p.Leu33Trp	missense	Exon 4 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.98T>G	p.Leu33Trp	missense	Exon 3 of 9	ENSP00000296557.4	P53367-1
	ARFIP1	ENST00000451320.6	TSL:1	c.98T>G	p.Leu33Trp	missense	Exon 3 of 9	ENSP00000395083.2	P53367-1
	ARFIP1	ENST00000356064.3	TSL:1	c.98T>G	p.Leu33Trp	missense	Exon 3 of 8	ENSP00000348360.3	P53367-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248376 AF XY: 0.00000745

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000101

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 AF: 0.00000281 AC: 4 AN: 1425270 Hom.: 0 Cov.: 26 AF XY: 0.00000281 AC XY: 2 AN XY: 711114

African (AFR) AF: 0.00 AC: 0 AN: 32486

American (AMR) AF: 0.00 AC: 0 AN: 44120

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25810

East Asian (EAS) AF: 0.00 AC: 0 AN: 39356

South Asian (SAS) AF: 0.00 AC: 0 AN: 84786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1080590

Other (OTH) AF: 0.0000169 AC: 1 AN: 59152

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000151

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	0.11
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.097	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	1.6	L
PhyloP100		5.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.73	P
Vest4		0.72
MutPred		0.34		Gain of glycosylation at S28 (P = 0.006)
MVP		0.91
MPC		0.91
ClinPred		0.86	D
GERP RS		5.9
Varity_R		0.33
gMVP		0.59
Mutation Taster		=82/18	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

dbSNP: rs1437956049; hg19: chr4-153784762;