Variant 10-114835597-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020940.4(FHIP2A):c.355C>G(p.Arg119Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 1,460,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

FHIP2A
NM_020940.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.93

Variant links:

Genes affected

FHIP2A (HGNC:29320): (FHF complex subunit HOOK interacting protein 2A)

FHIP2A links:

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ACMG classification

Classification made for transcript

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=0.4209262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIP2A	NM_020940.4 linkuse as main transcript	c.355C>G	p.Arg119Gly	missense_variant	4/17	ENST00000369248.9	NP_065991.3
FHIP2A	NM_001135051.2 linkuse as main transcript	c.355C>G	p.Arg119Gly	missense_variant	4/17		NP_001128523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FHIP2A	ENST00000369248.9 linkuse as main transcript	c.355C>G	p.Arg119Gly	missense_variant	4/17	1	NM_020940.4	ENSP00000358251.4	Q5W0V3-1
FHIP2A	ENST00000369250.7 linkuse as main transcript	c.355C>G	p.Arg119Gly	missense_variant	4/17	1		ENSP00000358253.3	Q5W0V3-2
FHIP2A	ENST00000710382.1 linkuse as main transcript	c.451C>G	p.Arg151Gly	missense_variant	4/17			ENSP00000518239.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250818

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135624

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460706

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000117

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2023

The c.355C>G (p.R119G) alteration is located in exon 4 (coding exon 4) of the FAM160B1 gene. This alteration results from a C to G substitution at nucleotide position 355, causing the arginine (R) at amino acid position 119 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.00051

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.011

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0070

D;D

Sift4G

Benign

0.15

T;D

Polyphen

0.016

B;B

Vest4

0.61

MutPred

0.63

Loss of catalytic residue at R119 (P = 0.0094);Loss of catalytic residue at R119 (P = 0.0094);

MVP

0.11

MPC

0.42

ClinPred

0.90

GERP RS

3.2

Varity_R

0.32

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over