Variant 1-62597843-AAAG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_014495.4(ANGPTL3):c.286_288delGAA(p.Glu96del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000135 in 1,605,168 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ANGPTL3
NM_014495.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 5.42

Variant links:

Genes affected

ANGPTL3 (HGNC:491): (angiopoietin like 3) This gene encodes a member of a family of secreted proteins that function in angiogenesis. The encoded protein, which is expressed predominantly in the liver, is further processed into an N-terminal coiled-coil domain-containing chain and a C-terminal fibrinogen chain. The N-terminal chain is important for lipid metabolism, while the C-terminal chain may be involved in angiogenesis. Mutations in this gene cause familial hypobetalipoproteinemia type 2. [provided by RefSeq, Aug 2015]

ANGPTL3 links:

DOCK7 (HGNC:19190): (dedicator of cytokinesis 7) The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that plays a role in axon formation and neuronal polarization. The encoded protein displays GEF activity toward RAC1 and RAC3 Rho small GTPases but not toward CDC42. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

DOCK7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_014495.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPTL3	NM_014495.4 link	c.286_288delGAA	p.Glu96del	conservative_inframe_deletion	1/7	ENST00000371129.4	NP_055310.1	Q9Y5C1
DOCK7	NM_001367561.1 link	c.1683-11222_1683-11220delCTT		intron_variant		ENST00000635253.2	NP_001354490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPTL3	ENST00000371129.4 link	c.286_288delGAA	p.Glu96del	conservative_inframe_deletion	1/7	1	NM_014495.4	ENSP00000360170.3		Q9Y5C1
DOCK7	ENST00000635253.2 link	c.1683-11222_1683-11220delCTT		intron_variant		5	NM_001367561.1	ENSP00000489124.1		Q96N67-1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000123

AC:

AN:

244136

Hom.:

AF XY:

0.000159

AC XY:

AN XY:

131894

show subpopulations

Gnomad AFR exome

AF:

0.000560

Gnomad AMR exome

AF:

0.0000605

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000242

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000120

AC:

174

AN:

1452900

Hom.:

AF XY:

0.000121

AC XY:

AN XY:

721796

show subpopulations

Gnomad4 AFR exome

AF:

0.00100

Gnomad4 AMR exome

AF:

0.0000692

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000202

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000893

Gnomad4 OTH exome

AF:

0.000284

GnomAD4 genome

AF:

0.000276

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.0000340

Hom.:

Bravo

AF:

0.000314

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial hypobetalipoproteinemia 2

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Oct 08, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	New York Genome Center	Mar 17, 2022	- -

Developmental and epileptic encephalopathy, 23

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

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