dbSNP rs3743853: FAHD1:p.Asp107Asn (chr16-1827557-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031208.4(FAHD1):c.319G>A(p.Asp107Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,238 control chromosomes in the GnomAD database, including 21,520 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1792 hom., cov: 33)

Exomes 𝑓: 0.16 ( 19728 hom. )

Consequence

FAHD1
NM_031208.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.72

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017102659).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAHD1	NM_031208.4 link	c.319G>A	p.Asp107Asn	missense_variant	Exon 1 of 1	ENST00000427358.5	NP_112485.2	Q6P587

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAHD1	ENST00000427358.5 link	c.319G>A	p.Asp107Asn	missense_variant	Exon 1 of 1	6	NM_031208.4	ENSP00000398053.3	Q6P587
FAHD1	ENST00000382668.8 link	c.319G>A	p.Asp107Asn	missense_variant	Exon 1 of 2	1		ENSP00000372114.5	Q6P587
FAHD1	ENST00000382666.6 link	c.319G>A	p.Asp107Asn	missense_variant	Exon 1 of 3	2		ENSP00000372112.5	Q6P587

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20234

AN:

152160

Hom.:

1794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.164

AC:

40962

AN:

249790

Hom.:

3739

AF XY:

0.168

AC XY:

22818

AN XY:

135426

show subpopulations

Gnomad AFR exome

AF:

0.0261

Gnomad AMR exome

AF:

0.163

Gnomad ASJ exome

AF:

0.127

Gnomad EAS exome

AF:

0.144

Gnomad SAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.163

GnomAD4 exome

AF:

0.160

AC:

233724

AN:

1460960

Hom.:

19728

Cov.:

AF XY:

0.162

AC XY:

117891

AN XY:

726792

show subpopulations

Gnomad4 AFR exome

AF:

0.0231

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.204

Gnomad4 FIN exome

AF:

0.255

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.133

AC:

20228

AN:

152278

Hom.:

1792

Cov.:

AF XY:

0.141

AC XY:

10533

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0295

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.160

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.271

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.148

Hom.:

2994

Bravo

AF:

0.117

TwinsUK

AF:

0.157

AC:

583

ALSPAC

AF:

0.158

AC:

608

ESP6500AA

AF:

0.0305

AC:

134

ESP6500EA

AF:

0.153

AC:

1320

ExAC

AF:

0.162

AC:

19617

Asia WGS

AF:

0.201

AC:

698

AN:

3478

EpiCase

AF:

0.153

EpiControl

AF:

0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;.;.;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

D;D;.;D

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.31

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

N;N;N;.

REVEL

Benign

0.25

Sift

Benign

0.35

T;T;T;.

Sift4G

Benign

0.43

T;T;T;T

Polyphen

0.0020

B;B;.;.

Vest4

0.047

MPC

0.14

ClinPred

0.068

GERP RS

1.5

Varity_R

0.21

gMVP

0.58

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over