Variant 16-1827483-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_031208.4(FAHD1):c.245T>A(p.Val82Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FAHD1
NM_031208.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

Variant links:

Genes affected

FAHD1 (HGNC:14169): (fumarylacetoacetate hydrolase domain containing 1) Enables acetylpyruvate hydrolase activity; fumarylpyruvate hydrolase activity; and oxaloacetate decarboxylase activity. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAHD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAHD1	NM_031208.4 linkuse as main transcript	c.245T>A	p.Val82Asp	missense_variant	1/1	ENST00000427358.5	NP_112485.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FAHD1	ENST00000427358.5 linkuse as main transcript	c.245T>A	p.Val82Asp	missense_variant	1/1		NM_031208.4	ENSP00000398053	P1
FAHD1	ENST00000382668.8 linkuse as main transcript	c.245T>A	p.Val82Asp	missense_variant	1/2	1		ENSP00000372114
FAHD1	ENST00000382666.6 linkuse as main transcript	c.245T>A	p.Val82Asp	missense_variant	1/3	2		ENSP00000372112

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

247918

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134892

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:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459922

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726160

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 02, 2023

The c.254T>A (p.V85D) alteration is located in exon 1 (coding exon 1) of the FAHD1 gene. This alteration results from a T to A substitution at nucleotide position 254, causing the valine (V) at amino acid position 85 to be replaced by an aspartic acid (D). 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

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Uncertain

0.74

D;.;.;.

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.0069

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D;.;D

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.77

D;D;D;D

MetaSVM

Uncertain

-0.26

MutationAssessor

Pathogenic

3.7

H;H;H;H

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.9

D;D;D;.

REVEL

Uncertain

0.34

Sift

Benign

0.096

T;D;D;.

Sift4G

Uncertain

0.017

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.48

MutPred

0.65

Loss of catalytic residue at V85 (P = 0.0231);Loss of catalytic residue at V85 (P = 0.0231);Loss of catalytic residue at V85 (P = 0.0231);Loss of catalytic residue at V85 (P = 0.0231);

MVP

0.49

MPC

0.83

ClinPred

0.84

GERP RS

3.4

Varity_R

0.94

gMVP

0.96

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

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