19-10093460-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_031917.3(ANGPTL6):c.1111G>A(p.Asp371Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,204 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 (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
ANGPTL6
NM_031917.3 missense
NM_031917.3 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 7.84
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]
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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=0.3336966).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANGPTL6 | NM_031917.3 | c.1111G>A | p.Asp371Asn | missense_variant | 5/6 | ENST00000253109.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANGPTL6 | ENST00000253109.5 | c.1111G>A | p.Asp371Asn | missense_variant | 5/6 | 1 | NM_031917.3 | P1 | |
ANGPTL6 | ENST00000592641.5 | c.1111G>A | p.Asp371Asn | missense_variant | 5/6 | 1 | P1 | ||
ANGPTL6 | ENST00000589181.5 | c.991G>A | p.Asp331Asn | missense_variant | 4/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152206Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251466Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135914
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727242
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74474
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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 | Oct 12, 2021 | The c.1111G>A (p.D371N) alteration is located in exon 5 (coding exon 4) of the ANGPTL6 gene. This alteration results from a G to A substitution at nucleotide position 1111, causing the aspartic acid (D) at amino acid position 371 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;.;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;.;N
REVEL
Uncertain
Sift
Uncertain
.;.;D
Sift4G
Uncertain
T;T;T
Polyphen
1.0
.;D;D
Vest4
MVP
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at