16-1827557-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAHD1	NM_031208.4	c.319G>T	p.Asp107Tyr	missense_variant	Exon 1 of 1	ENST00000427358.5	NP_112485.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAHD1	ENST00000427358.5	c.319G>T	p.Asp107Tyr	missense_variant	Exon 1 of 1	6	NM_031208.4	ENSP00000398053.3
FAHD1	ENST00000382668.8	c.319G>T	p.Asp107Tyr	missense_variant	Exon 1 of 2	1		ENSP00000372114.5
FAHD1	ENST00000382666.6	c.319G>T	p.Asp107Tyr	missense_variant	Exon 1 of 3	2		ENSP00000372112.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;.;D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.76	D;D;D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	1.4	L;L;L;L
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.5	D;D;D;.
REVEL	Uncertain	0.58
Sift	Uncertain	0.0020	D;D;D;.
Sift4G	Uncertain	0.024	D;D;D;D
Polyphen		0.98	D;D;.;.
Vest4		0.35
MutPred		0.42		Loss of disorder (P = 0.0427);Loss of disorder (P = 0.0427);Loss of disorder (P = 0.0427);Loss of disorder (P = 0.0427);
MVP		0.99
MPC		0.24
ClinPred		0.97	D
GERP RS		1.5
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

Publications

LitVar

Other links and lift over

dbSNP: rs3743853; hg19: chr16-1877558;