Variant rs2278426 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018687.7(ANGPTL8):c.175C>T(p.Arg59Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 1,604,966 control chromosomes in the GnomAD database, including 6,838 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1237 hom., cov: 32)

Exomes 𝑓: 0.062 ( 5601 hom. )

Consequence

ANGPTL8
NM_018687.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.623

Variant links:

Genes affected

ANGPTL8 (HGNC:24933): (angiopoietin like 8) Predicted to enable hormone activity. Involved in regulation of lipid metabolic process and triglyceride homeostasis. Acts upstream of or within positive regulation of protein processing and regulation of lipoprotein metabolic process. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ANGPTL8 links:

DOCK6 (HGNC:19189): (dedicator of cytokinesis 6) This gene encodes a member of the dedicator of cytokinesis (DOCK) family of atypical guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with small GTPases and are components of intracellular signaling networks. The encoded protein is a group C DOCK protein and plays a role in actin cytoskeletal reorganization by activating the Rho GTPases Cdc42 and Rac1. Mutations in this gene are associated with Adams-Oliver syndrome 2. [provided by RefSeq, Dec 2011]

DOCK6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037017763).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPTL8	NM_018687.7 linkuse as main transcript	c.175C>T	p.Arg59Trp	missense_variant	1/4	ENST00000252453.12	NP_061157.3	Q6UXH0
DOCK6	NM_020812.4 linkuse as main transcript	c.1644-1508G>A		intron_variant		ENST00000294618.12	NP_065863.2	Q96HP0B7Z9U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANGPTL8	ENST00000252453.12 linkuse as main transcript	c.175C>T	p.Arg59Trp	missense_variant	1/4	1	NM_018687.7	ENSP00000252453.7	Q6UXH0
DOCK6	ENST00000294618.12 linkuse as main transcript	c.1644-1508G>A		intron_variant		1	NM_020812.4	ENSP00000294618.6	Q96HP0
ANGPTL8	ENST00000591200.5 linkuse as main transcript	c.1-323C>T		intron_variant		1		ENSP00000464941.1	K7EIY2
DOCK6	ENST00000587656.6 linkuse as main transcript	c.1644-1508G>A		intron_variant		5		ENSP00000468638.2	K7ESB7

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16151

AN:

152050

Hom.:

1239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.252

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.0644

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0432

Gnomad OTH

AF:

0.0952

GnomAD3 exomes

AF:

0.113

AC:

25993

AN:

230988

Hom.:

2454

AF XY:

0.105

AC XY:

13241

AN XY:

125560

show subpopulations

Gnomad AFR exome

AF:

0.184

Gnomad AMR exome

AF:

0.265

Gnomad ASJ exome

AF:

0.0227

Gnomad EAS exome

AF:

0.258

Gnomad SAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.0650

Gnomad NFE exome

AF:

0.0432

Gnomad OTH exome

AF:

0.0805

GnomAD4 exome

AF:

0.0622

AC:

90311

AN:

1452798

Hom.:

5601

Cov.:

AF XY:

0.0641

AC XY:

46277

AN XY:

722036

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.0217

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.0650

Gnomad4 NFE exome

AF:

0.0378

Gnomad4 OTH exome

AF:

0.0708

GnomAD4 genome

AF:

0.106

AC:

16177

AN:

152168

Hom.:

1237

Cov.:

AF XY:

0.112

AC XY:

8364

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.252

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.0644

Gnomad4 NFE

AF:

0.0433

Gnomad4 OTH

AF:

0.0942

Alfa

AF:

0.0563

Hom.:

630

Bravo

AF:

0.120

TwinsUK

AF:

0.0405

AC:

150

ALSPAC

AF:

0.0363

AC:

140

ESP6500AA

AF:

0.171

AC:

673

ESP6500EA

AF:

0.0482

AC:

399

ExAC

AF:

0.104

AC:

12541

Asia WGS

AF:

0.163

AC:

570

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

T;T

Eigen

Benign

-0.075

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.77

T;.

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-1.1

PROVEAN

Pathogenic

-4.5

.;D

REVEL

Benign

0.090

Sift

Pathogenic

0.0

.;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;D

Vest4

0.12

MPC

0.70

ClinPred

0.030

GERP RS

3.5

Varity_R

0.31

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over