Variant 19-10096062-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_031917.3(ANGPTL6):c.502G>C(p.Ala168Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,325,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A168T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

ANGPTL6
NM_031917.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.696

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2861789).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPTL6	NM_031917.3 linkuse as main transcript	c.502G>C	p.Ala168Pro	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.502G>C	p.Ala168Pro	missense_variant	2/6	1	NM_031917.3	P1
ANGPTL6	ENST00000592641.5 linkuse as main transcript	c.502G>C	p.Ala168Pro	missense_variant	2/6	1		P1
ANGPTL6	ENST00000589181.5 linkuse as main transcript	c.502G>C	p.Ala168Pro	missense_variant	1/5	5
ANGPTL6	ENST00000586910.1 linkuse as main transcript	n.70G>C		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000151

AC:

AN:

1325820

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

658038

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:

0.0000274

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2022

The c.502G>C (p.A168P) alteration is located in exon 2 (coding exon 1) of the ANGPTL6 gene. This alteration results from a G to C substitution at nucleotide position 502, causing the alanine (A) at amino acid position 168 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.081

T;T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.72

T;.;T

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.8

.;L;L

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-2.1

.;.;N

REVEL

Benign

0.25

Sift

Uncertain

0.011

.;.;D

Sift4G

Uncertain

0.018

D;D;D

Polyphen

0.99

.;D;D

Vest4

0.20

MutPred

0.47

Loss of MoRF binding (P = 0.0437);Loss of MoRF binding (P = 0.0437);Loss of MoRF binding (P = 0.0437);

MVP

0.76

ClinPred

0.86

GERP RS

4.4

Varity_R

0.70

gMVP

0.68

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over