19-10093467-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.00

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]

ACMG classification

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 GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPTL6	NM_031917.3	c.1104C>T	p.Pro368=	synonymous_variant	5/6	ENST00000253109.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANGPTL6	ENST00000253109.5	c.1104C>T	p.Pro368=	synonymous_variant	5/6	1	NM_031917.3	P1
ANGPTL6	ENST00000592641.5	c.1104C>T	p.Pro368=	synonymous_variant	5/6	1		P1
ANGPTL6	ENST00000589181.5	c.984C>T	p.Pro328=	synonymous_variant	4/5	5

Frequencies

GnomAD3 genomes AF: 0.00633 AC: 963 AN: 152228 Hom.: 9 Cov.: 32

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

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

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

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	ANGPTL6: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

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

Other links and lift over

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