Variant chr19-10093499-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_031917.3(ANGPTL6):c.1072C>T(p.Arg358Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,614,168 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 11 hom., cov: 32)

Exomes 𝑓: 0.014 ( 184 hom. )

Consequence

ANGPTL6
NM_031917.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.95

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01036942).

BP6

Variant 19-10093499-G-A is Benign according to our data. Variant chr19-10093499-G-A is described in ClinVar as [Benign]. Clinvar id is 2649280.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0103 (1575/152314) while in subpopulation NFE AF= 0.017 (1157/68020). AF 95% confidence interval is 0.0162. There are 11 homozygotes in gnomad4. There are 741 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPTL6	NM_031917.3 linkuse as main transcript	c.1072C>T	p.Arg358Cys	missense_variant	5/6	ENST00000253109.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ANGPTL6	ENST00000253109.5 linkuse as main transcript	c.1072C>T	p.Arg358Cys	missense_variant	5/6	1	NM_031917.3	P1
ANGPTL6	ENST00000592641.5 linkuse as main transcript	c.1072C>T	p.Arg358Cys	missense_variant	5/6	1		P1
ANGPTL6	ENST00000589181.5 linkuse as main transcript	c.952C>T	p.Arg318Cys	missense_variant	4/5	5

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1576

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.0117

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0170

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.0114

AC:

2856

AN:

251354

Hom.:

AF XY:

0.0117

AC XY:

1589

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00308

Gnomad AMR exome

AF:

0.00555

Gnomad ASJ exome

AF:

0.000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00643

Gnomad FIN exome

AF:

0.0141

Gnomad NFE exome

AF:

0.0179

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0144

AC:

21123

AN:

1461854

Hom.:

184

Cov.:

AF XY:

0.0143

AC XY:

10366

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00254

Gnomad4 AMR exome

AF:

0.00537

Gnomad4 ASJ exome

AF:

0.000918

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00660

Gnomad4 FIN exome

AF:

0.0151

Gnomad4 NFE exome

AF:

0.0168

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.0103

AC:

1575

AN:

152314

Hom.:

Cov.:

AF XY:

0.00995

AC XY:

741

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00269

Gnomad4 AMR

AF:

0.00856

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00621

Gnomad4 FIN

AF:

0.0117

Gnomad4 NFE

AF:

0.0170

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.0137

Hom.:

Bravo

AF:

0.00969

TwinsUK

AF:

0.0156

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0143

AC:

123

ExAC

AF:

0.0124

AC:

1511

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0150

EpiControl

AF:

0.0157

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

ANGPTL6: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0068

LIST_S2

Benign

0.66

T;.;T

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.34

.;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.5

.;.;N

REVEL

Benign

0.24

Sift

Uncertain

0.024

.;.;D

Sift4G

Benign

0.13

T;T;T

Polyphen

0.17

.;B;B

Vest4

0.27

ClinPred

0.014

GERP RS

2.3

Varity_R

0.18

gMVP

0.60

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