Variant 2-97083983-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001320848.2(FAHD2B):c.847G>A(p.Val283Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

FAHD2B
NM_001320848.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.45

Variant links:

Genes affected

FAHD2B (HGNC:25318): (fumarylacetoacetate hydrolase domain containing 2B) Predicted to enable hydro-lyase activity. [provided by Alliance of Genome Resources, Apr 2022]

FAHD2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAHD2B	NM_001320848.2 linkuse as main transcript	c.847G>A	p.Val283Ile	missense_variant	8/9	ENST00000414820.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAHD2B	ENST00000414820.6 linkuse as main transcript	c.847G>A	p.Val283Ile	missense_variant	8/9	5	NM_001320848.2	P1
FAHD2B	ENST00000272610.3 linkuse as main transcript	c.847G>A	p.Val283Ile	missense_variant	7/8	1		P1
FAHD2B	ENST00000463096.5 linkuse as main transcript	n.1052G>A		non_coding_transcript_exon_variant	5/5	5
FAHD2B	ENST00000474849.1 linkuse as main transcript	n.415G>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250758

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135600

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461590

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ExAC

AF:

0.0000577

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

Dec 28, 2022

The c.847G>A (p.V283I) alteration is located in exon 7 (coding exon 6) of the FAHD2B gene. This alteration results from a G to A substitution at nucleotide position 847, causing the valine (V) at amino acid position 283 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

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;T

Eigen

Benign

0.12

Eigen_PC

Benign

-0.048

FATHMM_MKL

Benign

0.41

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Uncertain

0.73

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.88

N;N

REVEL

Uncertain

0.50

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.034

D;D

Polyphen

1.0

D;D

Vest4

0.30

MutPred

0.89

Gain of ubiquitination at K288 (P = 0.2348);Gain of ubiquitination at K288 (P = 0.2348);

MVP

0.86

MPC

0.22

ClinPred

0.17

GERP RS

1.3

Varity_R

0.079

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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