16-1827697-C-T

Variant names:

• chr16-1827697-C-T
• NM_031208.4:c.459C>T
• FAHD1 p.Leu153Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_031208.4(FAHD1):​c.459C>T​(p.Leu153Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: FAHD1 NM_031208.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=1.05 with no splicing effect.

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>T	p.Leu153Leu	synonymous	Exon 1 of 1	NP_112485.2	Q6P587-4
	FAHD1	NM_001018104.3		c.459C>T	p.Leu153Leu	synonymous	Exon 1 of 3	NP_001018114.2	Q6P587-3
	FAHD1	NM_001142398.2		c.459C>T	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>T	p.Leu153Leu	synonymous	Exon 1 of 1	ENSP00000398053.3	Q6P587-4
	FAHD1	ENST00000382668.8	TSL:1	c.459C>T	p.Leu153Leu	synonymous	Exon 1 of 2	ENSP00000372114.5	Q6P587-2
	FAHD1	ENST00000382666.6	TSL:2	c.459C>T	p.Leu153Leu	synonymous	Exon 1 of 3	ENSP00000372112.5	Q6P587-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.8
DANN	Benign	0.76
PhyloP100		1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-1877698;