chr11-6479274-C-T

Variant names:

• chr11-6479274-C-T
• rs1851463277
• NM_001376558.2:c.197-16G>A

Variant summary

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

The NM_001242854.3(ARFIP2):​c.280G>A​(p.Glu94Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARFIP2 NM_001242854.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97
• Publications: 0 publications found

Genes affected

ARFIP2 (HGNC:17160): (ADP ribosylation factor interacting protein 2) Enables several functions, including GTP-dependent protein binding activity; membrane curvature sensor activity; and phosphatidylinositol-4-phosphate binding activity. Involved in actin cytoskeleton organization. Located in cell cortex; ruffle; 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=0.14180446).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242854.3. 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
	ARFIP2	NM_001376558.2	MANE Select	c.197-16G>A		intron	N/A	NP_001363487.1	P53365-1
	ARFIP2	NM_001242854.3		c.280G>A	p.Glu94Lys	missense	Exon 4 of 8	NP_001229783.1	A0A087X1E4
	ARFIP2	NM_001376562.2		c.97G>A	p.Glu33Lys	missense	Exon 4 of 8	NP_001363491.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFIP2	ENST00000396777.8	TSL:2 MANE Select	c.197-16G>A		intron	N/A	ENSP00000379998.3	P53365-1
	ARFIP2	ENST00000254584.6	TSL:1	c.197-16G>A		intron	N/A	ENSP00000254584.2	P53365-1
	ARFIP2	ENST00000614314.4	TSL:2	c.280G>A	p.Glu94Lys	missense	Exon 4 of 8	ENSP00000484121.1	A0A087X1E4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.16
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.78
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.14	T
PhyloP100		2.0
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.92	T
Vest4		0.23
MVP		0.31
GERP RS		4.3
BranchPoint Hunter		3.0
gMVP		0.38
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1851463277; hg19: chr11-6500504;