Variant 10-114846242-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020940.4(FHIP2A):c.1273G>A(p.Val425Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000595 in 1,614,028 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00061 ( 1 hom. )

Consequence

FHIP2A
NM_020940.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.39

Variant links:

Genes affected

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

FHIP2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07362929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIP2A	NM_020940.4 linkuse as main transcript	c.1273G>A	p.Val425Ile	missense_variant	10/17	ENST00000369248.9	NP_065991.3
FHIP2A	NM_001135051.2 linkuse as main transcript	c.1273G>A	p.Val425Ile	missense_variant	10/17		NP_001128523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FHIP2A	ENST00000369248.9 linkuse as main transcript	c.1273G>A	p.Val425Ile	missense_variant	10/17	1	NM_020940.4	ENSP00000358251.4	Q5W0V3-1
FHIP2A	ENST00000369250.7 linkuse as main transcript	c.1273G>A	p.Val425Ile	missense_variant	10/17	1		ENSP00000358253.3	Q5W0V3-2
FHIP2A	ENST00000710382.1 linkuse as main transcript	c.1369G>A	p.Val457Ile	missense_variant	10/17			ENSP00000518239.1

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.000720

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000374

AC:

AN:

251226

Hom.:

AF XY:

0.000339

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000231

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:

0.000669

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000612

AC:

894

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000595

AC XY:

433

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000246

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:

0.000758

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000434

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.000359

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000453

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000711

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

Dec 03, 2024

The c.1273G>A (p.V425I) alteration is located in exon 10 (coding exon 10) of the FAM160B1 gene. This alteration results from a G to A substitution at nucleotide position 1273, causing the valine (V) at amino acid position 425 to be replaced by an isoleucine (I). 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

0.073

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.063

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.091

Sift

Benign

0.44

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.14

B;B

Vest4

0.17

MVP

0.11

MPC

0.21

ClinPred

0.031

GERP RS

5.3

Varity_R

0.038

gMVP

0.077

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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