Variant chr16-1827469-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_031208.4(FAHD1):c.231G>C(p.Lys77Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,252 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: 𝑓 0.000013 ( 0 hom., cov: 33)

Consequence

FAHD1
NM_031208.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34203976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAHD1	NM_031208.4 linkuse as main transcript	c.231G>C	p.Lys77Asn	missense_variant	1/1	ENST00000427358.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAHD1	ENST00000427358.5 linkuse as main transcript	c.231G>C	p.Lys77Asn	missense_variant	1/1		NM_031208.4	P1
FAHD1	ENST00000382668.8 linkuse as main transcript	c.231G>C	p.Lys77Asn	missense_variant	1/2	1
FAHD1	ENST00000382666.6 linkuse as main transcript	c.231G>C	p.Lys77Asn	missense_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000151

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 23, 2022

The c.240G>C (p.K80N) alteration is located in exon 1 (coding exon 1) of the FAHD1 gene. This alteration results from a G to C substitution at nucleotide position 240, causing the lysine (K) at amino acid position 80 to be replaced by an asparagine (N). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.75

D;.;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T;.;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Pathogenic

4.0

H;H;H;H

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.3

D;D;D;.

REVEL

Benign

0.10

Sift

Uncertain

0.0060

D;D;D;.

Sift4G

Uncertain

0.012

D;D;D;D

Polyphen

0.64

P;P;.;.

Vest4

0.14

MutPred

0.65

Loss of ubiquitination at K80 (P = 0.0341);Loss of ubiquitination at K80 (P = 0.0341);Loss of ubiquitination at K80 (P = 0.0341);Loss of ubiquitination at K80 (P = 0.0341);

MVP

0.55

MPC

0.30

ClinPred

0.65

GERP RS

0.13

Varity_R

0.61

gMVP

0.79

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