NM_031917.3:c.1055G>C

Variant names:

• chr19-10093516-C-G
• NM_031917.3:c.1055G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031917.3(ANGPTL6):​c.1055G>C​(p.Trp352Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANGPTL6 NM_031917.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.84
• Publications: 0 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]

ANGPTL6 Gene-Disease associations (from GenCC):

• intracranial berry aneurysm

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.93

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.1055G>C	p.Trp352Ser	missense	Exon 5 of 6	NP_114123.2
	ANGPTL6	NM_001321411.2		c.1055G>C	p.Trp352Ser	missense	Exon 5 of 6	NP_001308340.1	Q8NI99
	ANGPTL6	NM_001387347.1		c.1055G>C	p.Trp352Ser	missense	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.1055G>C	p.Trp352Ser	missense	Exon 5 of 6	ENSP00000253109.3	Q8NI99
	ANGPTL6	ENST00000592641.5	TSL:1	c.1055G>C	p.Trp352Ser	missense	Exon 5 of 6	ENSP00000467930.1	Q8NI99
	ANGPTL6	ENST00000890998.1		c.1055G>C	p.Trp352Ser	missense	Exon 6 of 7	ENSP00000561057.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.049	T
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-12	D
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.73		Gain of disorder (P = 9e-04)
MVP		0.92
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.96
gMVP		0.70
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

hg19: chr19-10204192;