19-10093467-G-A

Variant names:

• chr19-10093467-G-A
• rs76783850
• NM_031917.3:c.1104C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_031917.3(ANGPTL6):​c.1104C>T​(p.Pro368Pro) 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:3
• Conservation: PhyloP100: -3.00
• Publications: 4 publications found

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]

SHFL (HGNC:25649): (shiftless antiviral inhibitor of ribosomal frameshifting) This gene is an interferon stimulated gene (ISG) that inhibits viral replication. The encoded protein binds nucleic acids and inhibits programmed -1 ribosomal frameshifting required for translation by many RNA viruses. Viruses inhibited by the protein include Zika virus, dengue virus and the coronaviruses, SARS-CoV and SARS-CoV2. [provided by RefSeq, Aug 2021]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 AC in GnomAd4 at 963 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031917.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL6	NM_031917.3	MANE Select	c.1104C>T	p.Pro368Pro	synonymous	Exon 5 of 6	NP_114123.2
	ANGPTL6	NM_001321411.2		c.1104C>T	p.Pro368Pro	synonymous	Exon 5 of 6	NP_001308340.1	Q8NI99
	ANGPTL6	NM_001387347.1		c.1104C>T	p.Pro368Pro	synonymous	Exon 6 of 7	NP_001374276.1	Q8NI99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL6	ENST00000253109.5	TSL:1 MANE Select	c.1104C>T	p.Pro368Pro	synonymous	Exon 5 of 6	ENSP00000253109.3	Q8NI99
	ANGPTL6	ENST00000592641.5	TSL:1	c.1104C>T	p.Pro368Pro	synonymous	Exon 5 of 6	ENSP00000467930.1	Q8NI99
	ANGPTL6	ENST00000890998.1		c.1104C>T	p.Pro368Pro	synonymous	Exon 6 of 7	ENSP00000561057.1

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

GnomAD2 exomes AF: 0.00694 AC: 1746 AN: 251448 AF XY: 0.00684

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 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

African (AFR) AF: 0.00191 AC: 64 AN: 33480

American (AMR) AF: 0.00590 AC: 264 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000765 AC: 20 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000927 AC: 80 AN: 86254

European-Finnish (FIN) AF: 0.00386 AC: 206 AN: 53410

Middle Eastern (MID) AF: 0.00485 AC: 28 AN: 5768

European-Non Finnish (NFE) AF: 0.0111 AC: 12355 AN: 1112010

Other (OTH) AF: 0.00879 AC: 531 AN: 60396

GnomAD4 genome AF: 0.00632 AC: 963 AN: 152346 Hom.: 9 Cov.: 32 AF XY: 0.00591 AC XY: 440 AN XY: 74500

African (AFR) AF: 0.00216 AC: 90 AN: 41586

American (AMR) AF: 0.00817 AC: 125 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0101 AC: 684 AN: 68034

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.27
DANN	Benign	0.86
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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