rs368145555

Variant names:

• chr11-6477156-C-A
• rs368145555
• NM_001376558.2:c.983G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-6477156-C-A
• chr11-6477156-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001376558.2(ARFIP2):​c.983G>T​(p.Arg328Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R328Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARFIP2 NM_001376558.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.98

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28483915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARFIP2	NM_001376558.2	c.983G>T	p.Arg328Leu	missense_variant	Exon 8 of 8	ENST00000396777.8	NP_001363487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARFIP2	ENST00000396777.8	c.983G>T	p.Arg328Leu	missense_variant	Exon 8 of 8	2	NM_001376558.2	ENSP00000379998.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000406 AC: 1 AN: 246110 Hom.: 0 AF XY: 0.00000752 AC XY: 1 AN XY: 132928

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 6.85e-7 AC: 1 AN: 1459358 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725656

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;T;T;.;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Pathogenic	0.98	D;.;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.2	.;L;L;.;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-4.0	.;D;D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0040	.;D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D;D
Polyphen		0.093	.;B;B;.;.
Vest4		0.24
MutPred		0.32		.;Loss of disorder (P = 0.0523);Loss of disorder (P = 0.0523);.;.;
MVP		0.72
MPC		0.73
ClinPred		0.95	D
GERP RS		5.0
Varity_R		0.33
gMVP		0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs368145555; hg19: chr11-6498386;