19-10093467-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_031917.3(ANGPTL6):​c.1104C>T​(p.Pro368=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00899 in 1,614,224 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 9 hom., cov: 32)
Exomes 𝑓: 0.0093 ( 82 hom. )

Consequence

ANGPTL6
NM_031917.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.00
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 19-10093467-G-A is Benign according to our data. Variant chr19-10093467-G-A is described in ClinVar as [Benign]. Clinvar id is 778156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANGPTL6NM_031917.3 linkuse as main transcriptc.1104C>T p.Pro368= synonymous_variant 5/6 ENST00000253109.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANGPTL6ENST00000253109.5 linkuse as main transcriptc.1104C>T p.Pro368= synonymous_variant 5/61 NM_031917.3 P1
ANGPTL6ENST00000592641.5 linkuse as main transcriptc.1104C>T p.Pro368= synonymous_variant 5/61 P1
ANGPTL6ENST00000589181.5 linkuse as main transcriptc.984C>T p.Pro328= synonymous_variant 4/55

Frequencies

GnomAD3 genomes
AF:
0.00633
AC:
963
AN:
152228
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00217
Gnomad AMI
AF:
0.0143
Gnomad AMR
AF:
0.00818
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00207
Gnomad FIN
AF:
0.00245
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0101
Gnomad OTH
AF:
0.00525
GnomAD3 exomes
AF:
0.00694
AC:
1746
AN:
251448
Hom.:
15
AF XY:
0.00684
AC XY:
929
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00234
Gnomad AMR exome
AF:
0.00613
Gnomad ASJ exome
AF:
0.000397
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000947
Gnomad FIN exome
AF:
0.00282
Gnomad NFE exome
AF:
0.0118
Gnomad OTH exome
AF:
0.00929
GnomAD4 exome
AF:
0.00927
AC:
13550
AN:
1461878
Hom.:
82
Cov.:
31
AF XY:
0.00901
AC XY:
6550
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00191
Gnomad4 AMR exome
AF:
0.00590
Gnomad4 ASJ exome
AF:
0.000765
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000927
Gnomad4 FIN exome
AF:
0.00386
Gnomad4 NFE exome
AF:
0.0111
Gnomad4 OTH exome
AF:
0.00879
GnomAD4 genome
AF:
0.00632
AC:
963
AN:
152346
Hom.:
9
Cov.:
32
AF XY:
0.00591
AC XY:
440
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00216
Gnomad4 AMR
AF:
0.00817
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00207
Gnomad4 FIN
AF:
0.00245
Gnomad4 NFE
AF:
0.0101
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00902
Hom.:
3
Bravo
AF:
0.00689
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.0113
EpiControl
AF:
0.0119

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2024ANGPTL6: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
0.27
DANN
Benign
0.86

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.

Other links and lift over

dbSNP: rs76783850; hg19: chr19-10204143; COSMIC: COSV53463782; COSMIC: COSV53463782; API