rs1383217858

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031917.3(ANGPTL6):c.371C>T(p.Pro124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000323 in 1,240,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

ANGPTL6
NM_031917.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.127

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

intracranial berry aneurysm
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ANGPTL6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09550047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPTL6	NM_031917.3 link	c.371C>T	p.Pro124Leu	missense_variant	Exon 2 of 6	ENST00000253109.5	NP_114123.2	Q8NI99A0A024R7A9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ANGPTL6	ENST00000253109.5 link	c.371C>T	p.Pro124Leu	missense_variant	Exon 2 of 6	1	NM_031917.3	ENSP00000253109.3	Q8NI99
ANGPTL6	ENST00000592641.5 link	c.371C>T	p.Pro124Leu	missense_variant	Exon 2 of 6	1		ENSP00000467930.1	Q8NI99
ANGPTL6	ENST00000589181.5 link	c.371C>T	p.Pro124Leu	missense_variant	Exon 1 of 5	5		ENSP00000465597.1	K7EKF6
ANGPTL6	ENST00000586910.1 link	n.-62C>T		upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000184

AC:

AN:

1089760

Hom.:

Cov.:

AF XY:

0.00000193

AC XY:

AN XY:

517848

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22542

American (AMR)

AF:

0.00

AC:

AN:

8096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14048

East Asian (EAS)

AF:

0.00

AC:

AN:

25794

South Asian (SAS)

AF:

0.00

AC:

AN:

25644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22130

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2914

European-Non Finnish (NFE)

AF:

0.00000216

AC:

AN:

925002

Other (OTH)

AF:

0.00

AC:

AN:

43590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150506

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73500

show subpopulations

African (AFR)

AF:

0.0000486

AC:

AN:

41182

American (AMR)

AF:

0.00

AC:

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67498

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.371C>T (p.P124L) alteration is located in exon 2 (coding exon 1) of the ANGPTL6 gene. This alteration results from a C to T substitution at nucleotide position 371, causing the proline (P) at amino acid position 124 to be replaced by a leucine (L). 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

Benign

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.3

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0062

T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.39

T;.;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.096

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N;N

PhyloP100

-0.13

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.46

.;.;N

REVEL

Benign

0.10

Sift

Benign

0.15

.;.;T

Sift4G

Uncertain

0.035

D;D;D

Polyphen

0.0010

.;B;B

Vest4

0.086

MutPred

0.17

Gain of catalytic residue at P124 (P = 0.0374);Gain of catalytic residue at P124 (P = 0.0374);Gain of catalytic residue at P124 (P = 0.0374);

MVP

0.34

ClinPred

0.11

GERP RS

2.0

PromoterAI

-0.014

Neutral

(source)

Varity_R

0.026

gMVP

0.17

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1383217858

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over