Variant 19-10096172-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_031917.3(ANGPTL6):c.392A>T(p.Glu131Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,298,166 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 5 hom. )

Consequence

ANGPTL6
NM_031917.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.20

Variant links:

Genes affected

ANGPTL6 (HGNC:23140): (angiopoietin like 6) Predicted to enable signaling receptor binding activity. Predicted to be involved in angiogenesis and cell differentiation. Located in extracellular exosome. Part of collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

ANGPTL6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03135103).

BP6

Variant 19-10096172-T-A is Benign according to our data. Variant chr19-10096172-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3048138.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPTL6	NM_031917.3 linkuse as main transcript	c.392A>T	p.Glu131Val	missense_variant	2/6	ENST00000253109.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ANGPTL6	ENST00000253109.5 linkuse as main transcript	c.392A>T	p.Glu131Val	missense_variant	2/6	1	NM_031917.3	P1
ANGPTL6	ENST00000592641.5 linkuse as main transcript	c.392A>T	p.Glu131Val	missense_variant	2/6	1		P1
ANGPTL6	ENST00000589181.5 linkuse as main transcript	c.392A>T	p.Glu131Val	missense_variant	1/5	5
ANGPTL6	ENST00000586910.1 linkuse as main transcript			upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

238

AN:

151018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000509

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00218

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000196

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00263

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000742

AC:

AN:

8084

Hom.:

AF XY:

0.000389

AC XY:

AN XY:

5140

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00275

AC:

3158

AN:

1147042

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

1448

AN XY:

552568

show subpopulations

Gnomad4 AFR exome

AF:

0.000427

Gnomad4 AMR exome

AF:

0.00258

Gnomad4 ASJ exome

AF:

0.0000630

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000275

Gnomad4 NFE exome

AF:

0.00314

Gnomad4 OTH exome

AF:

0.00251

GnomAD4 genome

AF:

0.00157

AC:

238

AN:

151124

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

104

AN XY:

73864

show subpopulations

Gnomad4 AFR

AF:

0.000508

Gnomad4 AMR

AF:

0.00217

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000196

Gnomad4 NFE

AF:

0.00263

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00229

Hom.:

Bravo

AF:

0.00174

ExAC

AF:

0.000546

AC:

Asia WGS

AF:

0.000290

AC:

AN:

3462

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ANGPTL6-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.27

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.040

T;T;T

Eigen

Benign

-0.070

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.50

T;.;T

M_CAP

Pathogenic

0.69

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-0.86

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Pathogenic

0.91

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.98

.;D;D

Vest4

0.21

MVP

0.61

ClinPred

0.15

GERP RS

4.0

Varity_R

0.24

gMVP

0.45

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