chr19-10094807-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031917.3(ANGPTL6):​c.714G>T​(p.Met238Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ANGPTL6
NM_031917.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.715
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.071205854).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ANGPTL6NM_031917.3 linkuse as main transcriptc.714G>T p.Met238Ile missense_variant 3/6 ENST00000253109.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANGPTL6ENST00000253109.5 linkuse as main transcriptc.714G>T p.Met238Ile missense_variant 3/61 NM_031917.3 P1
ANGPTL6ENST00000592641.5 linkuse as main transcriptc.714G>T p.Met238Ile missense_variant 3/61 P1
ANGPTL6ENST00000589181.5 linkuse as main transcriptc.714G>T p.Met238Ile missense_variant 2/55
ANGPTL6ENST00000586910.1 linkuse as main transcriptn.282G>T non_coding_transcript_exon_variant 2/24

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251448
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727238
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
7.9
DANN
Benign
0.61
DEOGEN2
Benign
0.0076
T;T;T
Eigen
Benign
-0.91
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.47
T;.;T
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.071
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.11
.;.;N
REVEL
Benign
0.092
Sift
Benign
0.48
.;.;T
Sift4G
Benign
0.44
T;T;T
Polyphen
0.0
.;B;B
Vest4
0.16
MutPred
0.15
Loss of glycosylation at P237 (P = 0.0972);Loss of glycosylation at P237 (P = 0.0972);Loss of glycosylation at P237 (P = 0.0972);
MVP
0.44
ClinPred
0.031
T
GERP RS
2.9
Varity_R
0.062
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1260808165; hg19: chr19-10205483; API