rs765424213

Variant names:

• chr11-6480346-G-A
• rs765424213
• NM_001376558.2:c.76C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001376558.2(ARFIP2):​c.76C>T​(p.Pro26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: ARFIP2 NM_001376558.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12622443).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376558.2. 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.76C>T	p.Pro26Ser	missense	Exon 2 of 8	NP_001363487.1	P53365-1
	ARFIP2	NM_001242854.3		c.76C>T	p.Pro26Ser	missense	Exon 2 of 8	NP_001229783.1	A0A087X1E4
	ARFIP2	NM_012402.5		c.76C>T	p.Pro26Ser	missense	Exon 2 of 8	NP_036534.1	P53365-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARFIP2	ENST00000396777.8	TSL:2 MANE Select	c.76C>T	p.Pro26Ser	missense	Exon 2 of 8	ENSP00000379998.3	P53365-1
	ARFIP2	ENST00000254584.6	TSL:1	c.76C>T	p.Pro26Ser	missense	Exon 2 of 8	ENSP00000254584.2	P53365-1
	ARFIP2	ENST00000614314.4	TSL:2	c.76C>T	p.Pro26Ser	missense	Exon 2 of 8	ENSP00000484121.1	A0A087X1E4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152206 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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 250048 AF XY: 0.0000370

Gnomad AFR exome AF: 0.00

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: 0.0000531

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461208 Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 726836

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111730

Other (OTH) AF: 0.0000331 AC: 2 AN: 60360

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41448

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: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000545

EpiControl AF: 0.0000594

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	0.082
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.029
Eigen_PC	Benign	0.099
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	0.62	T
Polyphen		0.67	P
Vest4		0.43
MutPred		0.17		Gain of phosphorylation at P26 (P = 0.0271)
MVP		0.67
MPC		0.59
ClinPred		0.12	T
GERP RS		5.1
Varity_R		0.12
gMVP		0.49
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs765424213; hg19: chr11-6501576;