19-10093460-C-T

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

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84
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 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
ANGPTL6NM_031917.3 linkuse as main transcriptc.1111G>A p.Asp371Asn missense_variant 5/6 ENST00000253109.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANGPTL6ENST00000253109.5 linkuse as main transcriptc.1111G>A p.Asp371Asn missense_variant 5/61 NM_031917.3 P1
ANGPTL6ENST00000592641.5 linkuse as main transcriptc.1111G>A p.Asp371Asn missense_variant 5/61 P1
ANGPTL6ENST00000589181.5 linkuse as main transcriptc.991G>A p.Asp331Asn missense_variant 4/55

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152206
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251466
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000173
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152324
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000474
Bravo
AF:
0.00000756
ExAC
AF:
0.0000247
AC:
3

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 submitterclinical testingAmbry GeneticsOct 12, 2021The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.29
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.013
T;T;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Benign
0.60
D
LIST_S2
Uncertain
0.91
D;.;D
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.33
T;T;T
MetaSVM
Uncertain
-0.0097
T
MutationAssessor
Benign
1.6
.;L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.6
.;.;N
REVEL
Uncertain
0.37
Sift
Uncertain
0.0060
.;.;D
Sift4G
Uncertain
0.058
T;T;T
Polyphen
1.0
.;D;D
Vest4
0.43
MVP
0.91
ClinPred
0.41
T
GERP RS
4.5
Varity_R
0.68
gMVP
0.59

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: rs200296130; hg19: chr19-10204136; COSMIC: COSV53462351; COSMIC: COSV53462351; API