chr16-1827557-G-A

Variant names:

• chr16-1827557-G-A
• rs3743853
• NM_031208.4:c.319G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/21 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 38 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031208.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAHD1	NM_031208.4	MANE Select	c.319G>A	p.Asp107Asn	missense	Exon 1 of 1	NP_112485.2	Q6P587-4
	FAHD1	NM_001018104.3		c.319G>A	p.Asp107Asn	missense	Exon 1 of 3	NP_001018114.2	Q6P587-3
	FAHD1	NM_001142398.2		c.319G>A	p.Asp107Asn	missense	Exon 1 of 2	NP_001135870.2	Q6P587-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAHD1	ENST00000427358.5	TSL:6 MANE Select	c.319G>A	p.Asp107Asn	missense	Exon 1 of 1	ENSP00000398053.3	Q6P587-4
	FAHD1	ENST00000382668.8	TSL:1	c.319G>A	p.Asp107Asn	missense	Exon 1 of 2	ENSP00000372114.5	Q6P587-2
	FAHD1	ENST00000382666.6	TSL:2	c.319G>A	p.Asp107Asn	missense	Exon 1 of 3	ENSP00000372112.5	Q6P587-3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20234 AN: 152160 Hom.: 1794 Cov.: 33

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

GnomAD2 exomes AF: 0.164 AC: 40962 AN: 249790 AF XY: 0.168

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 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.: 33 AF XY: 0.162 AC XY: 117891 AN XY: 726792

African (AFR) AF: 0.0231 AC: 773 AN: 33480

American (AMR) AF: 0.169 AC: 7553 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 3357 AN: 26136

East Asian (EAS) AF: 0.191 AC: 7584 AN: 39700

South Asian (SAS) AF: 0.204 AC: 17608 AN: 86254

European-Finnish (FIN) AF: 0.255 AC: 13430 AN: 52632

Middle Eastern (MID) AF: 0.118 AC: 680 AN: 5764

European-Non Finnish (NFE) AF: 0.156 AC: 173394 AN: 1111914

Other (OTH) AF: 0.155 AC: 9345 AN: 60378

GnomAD4 genome AF: 0.133 AC: 20228 AN: 152278 Hom.: 1792 Cov.: 33 AF XY: 0.141 AC XY: 10533 AN XY: 74444

African (AFR) AF: 0.0295 AC: 1225 AN: 41584

American (AMR) AF: 0.169 AC: 2581 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3472

East Asian (EAS) AF: 0.160 AC: 830 AN: 5172

South Asian (SAS) AF: 0.197 AC: 953 AN: 4830

European-Finnish (FIN) AF: 0.271 AC: 2867 AN: 10594

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10858 AN: 68020

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.143 Hom.: 4533

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.31	N
PhyloP100		2.7
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.25
Sift	Benign	0.35	T
Sift4G	Benign	0.43	T
Polyphen		0.0020	B
Vest4		0.047
MPC		0.14
ClinPred		0.068	T
GERP RS		1.5
PromoterAI		-0.0054	Neutral
Varity_R		0.21
gMVP		0.58
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3743853; hg19: chr16-1877558; COSMIC: COSV66899490; COSMIC: COSV66899490;