Genetic Variant FAH:c.81+38_81+39insGAGGGG (chr15-80153170-A-AGGGGAG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_000137.4(FAH):c.81+38_81+39insGAGGGG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 20)

Exomes 𝑓: 0.000046 ( 1 hom. )

Consequence

FAH
NM_000137.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.921

Publications

0 publications found

Variant links:

Genes affected

FAH (HGNC:3579): (fumarylacetoacetate hydrolase) Predicted to enable fumarylacetoacetase activity. Predicted to be involved in L-phenylalanine catabolic process; homogentisate catabolic process; and tyrosine catabolic process. Predicted to act upstream of or within arginine catabolic process. Located in extracellular exosome. Implicated in tyrosinemia type I. [provided by Alliance of Genome Resources, Apr 2022]

FAH Gene-Disease associations (from GenCC):

tyrosinemia type I
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine, G2P, Orphanet, Ambry Genetics, ClinGen

FAH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
FAH	NM_000137.4 link	c.81+38_81+39insGAGGGG	intron_variant	Intron 1 of 13	ENST00000561421.6	NP_000128.1
FAH	NM_001374377.1 link	c.81+38_81+39insGAGGGG	intron_variant	Intron 2 of 14		NP_001361306.1
FAH	NM_001374380.1 link	c.81+38_81+39insGAGGGG	intron_variant	Intron 2 of 14		NP_001361309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAH	ENST00000561421.6 link	c.81+35_81+36insGGGGAG		intron_variant	Intron 1 of 13	1	NM_000137.4	ENSP00000453347.2

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

111914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000172

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000179

AC:

AN:

234040

AF XY:

0.000187

show subpopulations

Gnomad AFR exome

AF:

0.0000850

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00243

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000464

AC:

AN:

1292180

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

650158

show subpopulations

African (AFR)

AF:

0.0000416

AC:

AN:

24030

American (AMR)

AF:

0.00

AC:

AN:

43356

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24628

East Asian (EAS)

AF:

0.00113

AC:

AN:

38144

South Asian (SAS)

AF:

0.00

AC:

AN:

82106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5374

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

972444

Other (OTH)

AF:

0.0000373

AC:

AN:

53612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000116

AC:

AN:

111982

Hom.:

Cov.:

AF XY:

0.000184

AC XY:

AN XY:

54334

show subpopulations

African (AFR)

AF:

0.000135

AC:

AN:

22300

American (AMR)

AF:

0.00

AC:

AN:

10838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2998

East Asian (EAS)

AF:

0.00270

AC:

AN:

3334

South Asian (SAS)

AF:

0.00

AC:

AN:

3678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.0000172

AC:

AN:

58072

Other (OTH)

AF:

0.00

AC:

AN:

1580

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.92

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over