rs774230768

Variant names:

• chr5-73051352-A-G
• rs774230768
• NM_138782.3:c.943A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-73051352-A-G
• chr5-73051352-A-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_138782.3(FCHO2):​c.943A>G​(p.Ile315Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000072 in 1,527,166 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I315F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: FCHO2 NM_138782.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

Genes affected

FCHO2 (HGNC:25180): (FCH and mu domain containing endocytic adaptor 2) Enables identical protein binding activity. Involved in clathrin coat assembly and clathrin-dependent endocytosis. Located in clathrin-coated pit and clathrin-coated vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042099565).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138782.3. 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
	FCHO2	NM_138782.3	MANE Select	c.943A>G	p.Ile315Val	missense	Exon 12 of 26	NP_620137.2	Q0JRZ9-1
	FCHO2	NM_001146032.2		c.844A>G	p.Ile282Val	missense	Exon 11 of 25	NP_001139504.1	Q0JRZ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCHO2	ENST00000430046.7	TSL:1 MANE Select	c.943A>G	p.Ile315Val	missense	Exon 12 of 26	ENSP00000393776.2	Q0JRZ9-1
	FCHO2	ENST00000956652.1		c.943A>G	p.Ile315Val	missense	Exon 12 of 27	ENSP00000626711.1
	FCHO2	ENST00000956650.1		c.943A>G	p.Ile315Val	missense	Exon 12 of 27	ENSP00000626709.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151980 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: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000666 AC: 1 AN: 150200 AF XY: 0.0000126

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: 0.0000168

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000654 AC: 9 AN: 1375186 Hom.: 0 Cov.: 27 AF XY: 0.00000736 AC XY: 5 AN XY: 678988

African (AFR) AF: 0.00 AC: 0 AN: 30526

American (AMR) AF: 0.00 AC: 0 AN: 33496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24904

East Asian (EAS) AF: 0.00 AC: 0 AN: 35374

South Asian (SAS) AF: 0.00 AC: 0 AN: 76818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5636

European-Non Finnish (NFE) AF: 0.00000847 AC: 9 AN: 1062200

Other (OTH) AF: 0.00 AC: 0 AN: 57116

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151980 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74232

African (AFR) AF: 0.00 AC: 0 AN: 41368

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00316 AC: 1 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000189

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	Benign	-0.24	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.52
DEOGEN2	Benign	0.00043	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.091
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.028
Sift	Benign	0.97	T
Sift4G	Benign	0.57	T
Polyphen		0.0010	B
Vest4		0.066
MVP		0.22
MPC		0.20
ClinPred		0.073	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.033
gMVP		0.037
Mutation Taster		=98/2	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: rs774230768; hg19: chr5-72347179;