16-1827557-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031208.4(FAHD1):​c.319G>T​(p.Asp107Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

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>T	p.Asp107Tyr	missense	Exon 1 of 1	NP_112485.2	Q6P587-4
	FAHD1	NM_001018104.3		c.319G>T	p.Asp107Tyr	missense	Exon 1 of 3	NP_001018114.2	Q6P587-3
	FAHD1	NM_001142398.2		c.319G>T	p.Asp107Tyr	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>T	p.Asp107Tyr	missense	Exon 1 of 1	ENSP00000398053.3	Q6P587-4
	FAHD1	ENST00000382668.8	TSL:1	c.319G>T	p.Asp107Tyr	missense	Exon 1 of 2	ENSP00000372114.5	Q6P587-2
	FAHD1	ENST00000382666.6	TSL:2	c.319G>T	p.Asp107Tyr	missense	Exon 1 of 3	ENSP00000372112.5	Q6P587-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 4533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.61	D
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	1.4	L
PhyloP100		2.7
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.024	D
Polyphen		0.98	D
Vest4		0.35
MutPred		0.42		Loss of disorder (P = 0.0427)
MVP		0.99
MPC		0.24
ClinPred		0.97	D
GERP RS		1.5
PromoterAI		0.0063	Neutral
Varity_R		0.71
gMVP		0.74

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;