NM_031208.4:c.459C>G

Variant names:

• chr16-1827697-C-G
• rs3743852
• NM_031208.4:c.459C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031208.4(FAHD1):​c.459C>G​(p.Leu153Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,974 control chromosomes in the GnomAD database, including 15,371 homozygotes. In-silico tool predicts 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 (1250 hom., cov: 33)
  • Exomes 𝑓: 0.14 (14121 hom.)
• Consequence: FAHD1 NM_031208.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 11 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 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.459C>G	p.Leu153Leu	synonymous	Exon 1 of 1	NP_112485.2	Q6P587-4
	FAHD1	NM_001018104.3		c.459C>G	p.Leu153Leu	synonymous	Exon 1 of 3	NP_001018114.2	Q6P587-3
	FAHD1	NM_001142398.2		c.459C>G	p.Leu153Leu	synonymous	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.459C>G	p.Leu153Leu	synonymous	Exon 1 of 1	ENSP00000398053.3	Q6P587-4
	FAHD1	ENST00000382668.8	TSL:1	c.459C>G	p.Leu153Leu	synonymous	Exon 1 of 2	ENSP00000372114.5	Q6P587-2
	FAHD1	ENST00000382666.6	TSL:2	c.459C>G	p.Leu153Leu	synonymous	Exon 1 of 3	ENSP00000372112.5	Q6P587-3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19310 AN: 152148 Hom.: 1251 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.127 AC: 31916 AN: 251092 AF XY: 0.129

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.0843

Gnomad ASJ exome AF: 0.138

Gnomad EAS exome AF: 0.105

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.137 AC: 199901 AN: 1461708 Hom.: 14121 Cov.: 34 AF XY: 0.138 AC XY: 100011 AN XY: 727158

African (AFR) AF: 0.104 AC: 3479 AN: 33478

American (AMR) AF: 0.0874 AC: 3909 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3699 AN: 26134

East Asian (EAS) AF: 0.146 AC: 5799 AN: 39698

South Asian (SAS) AF: 0.138 AC: 11916 AN: 86256

European-Finnish (FIN) AF: 0.147 AC: 7846 AN: 53334

Middle Eastern (MID) AF: 0.147 AC: 847 AN: 5766

European-Non Finnish (NFE) AF: 0.139 AC: 154359 AN: 1111934

Other (OTH) AF: 0.133 AC: 8047 AN: 60392

GnomAD4 genome AF: 0.127 AC: 19315 AN: 152266 Hom.: 1250 Cov.: 33 AF XY: 0.127 AC XY: 9421 AN XY: 74440

African (AFR) AF: 0.104 AC: 4311 AN: 41544

American (AMR) AF: 0.124 AC: 1893 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3472

East Asian (EAS) AF: 0.119 AC: 614 AN: 5174

South Asian (SAS) AF: 0.142 AC: 687 AN: 4830

European-Finnish (FIN) AF: 0.146 AC: 1551 AN: 10604

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9416 AN: 68024

Other (OTH) AF: 0.134 AC: 284 AN: 2116

Alfa AF: 0.134 Hom.: 465

Bravo AF: 0.123

Asia WGS AF: 0.0940 AC: 329 AN: 3478

EpiCase AF: 0.133

EpiControl AF: 0.133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.3
DANN	Benign	0.65
PhyloP100		1.1
Mutation Taster		=100/0	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: rs3743852; hg19: chr16-1877698; COSMIC: COSV66900768; COSMIC: COSV66900768;