11-6477809-C-T

Variant names:

• chr11-6477809-C-T
• rs758641222
• NM_001376558.2:c.779G>A

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.779G>A​(p.Ser260Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ARFIP2 NM_001376558.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13033289).
• BS2: High AC in GnomAdExome4 at 7 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.779G>A	p.Ser260Asn	missense	Exon 7 of 8	NP_001363487.1	P53365-1
	ARFIP2	NM_001242854.3		c.878G>A	p.Ser293Asn	missense	Exon 7 of 8	NP_001229783.1	A0A087X1E4
	ARFIP2	NM_012402.5		c.779G>A	p.Ser260Asn	missense	Exon 7 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.779G>A	p.Ser260Asn	missense	Exon 7 of 8	ENSP00000379998.3	P53365-1
	ARFIP2	ENST00000254584.6	TSL:1	c.779G>A	p.Ser260Asn	missense	Exon 7 of 8	ENSP00000254584.2	P53365-1
	ARFIP2	ENST00000614314.4	TSL:2	c.878G>A	p.Ser293Asn	missense	Exon 7 of 8	ENSP00000484121.1	A0A087X1E4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251452 AF XY: 0.0000147

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111972

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74254

African (AFR) AF: 0.00 AC: 0 AN: 41394

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.081
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	-0.20	N
PhyloP100		1.2
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.16
Sift	Benign	0.24	T
Sift4G	Benign	0.17	T
Polyphen		0.015	B
Vest4		0.41
MutPred		0.39		Gain of helix (P = 0.0082)
MVP		0.51
MPC		0.51
ClinPred		0.16	T
GERP RS		4.6
Varity_R		0.27
gMVP		0.22
Mutation Taster		=83/17	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: rs758641222; hg19: chr11-6499039;