Genetic Variant FAXDC2:p.Thr306ProfsTer100 (chr5-154820402-TC-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032385.5(FAXDC2):c.915delG(p.Thr306ProfsTer100) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,612,890 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 1 hom. )

Consequence

FAXDC2
NM_032385.5 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.790

Variant links:

Genes affected

FAXDC2 (HGNC:1334): (fatty acid hydroxylase domain containing 2) Predicted to enable C-4 methylsterol oxidase activity. Involved in positive regulation of megakaryocyte differentiation and positive regulation of protein phosphorylation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAXDC2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAXDC2	NM_032385.5 link	c.915delG	p.Thr306ProfsTer100	frameshift_variant	Exon 9 of 9	ENST00000326080.10	NP_115761.2	Q96IV6-1
FAXDC2	XM_006714753.3 link	c.915delG	p.Thr306ProfsTer100	frameshift_variant	Exon 10 of 10		XP_006714816.1	Q96IV6-1
FAXDC2	XM_047416652.1 link	c.495delG	p.Thr166ProfsTer100	frameshift_variant	Exon 6 of 6		XP_047272608.1
FAXDC2	XM_047416654.1 link	c.495delG	p.Thr166ProfsTer100	frameshift_variant	Exon 5 of 5		XP_047272610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAXDC2	ENST00000326080.10 link	c.915delG	p.Thr306ProfsTer100	frameshift_variant	Exon 9 of 9	1	NM_032385.5	ENSP00000320604.5		Q96IV6-1

Frequencies

GnomAD3 genomes

AF:

0.0000264

AC:

AN:

151722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000528

AC:

AN:

246106

Hom.:

AF XY:

0.0000673

AC XY:

AN XY:

133632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461168

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

726956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000264

AC:

AN:

151722

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74098

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autism

Uncertain:1

Centre for Addiction & Mental Health, Centre for Addiction & Mental Health

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

Gene not previously associated with disease; independent supportng evidence needed -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over