19-10093516-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANGPTL6	NM_031917.3	c.1055G>C	p.Trp352Ser	missense_variant	Exon 5 of 6	ENST00000253109.5	NP_114123.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPTL6	ENST00000253109.5	c.1055G>C	p.Trp352Ser	missense_variant	Exon 5 of 6	1	NM_031917.3	ENSP00000253109.3
ANGPTL6	ENST00000592641.5	c.1055G>C	p.Trp352Ser	missense_variant	Exon 5 of 6	1		ENSP00000467930.1
ANGPTL6	ENST00000589181.5	c.935G>C	p.Trp312Ser	missense_variant	Exon 4 of 5	5		ENSP00000465597.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1055G>C (p.W352S) alteration is located in exon 5 (coding exon 4) of the ANGPTL6 gene. This alteration results from a G to C substitution at nucleotide position 1055, causing the tryptophan (W) at amino acid position 352 to be replaced by a serine (S). 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	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;T;T
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.89	D;.;T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Uncertain	2.7	.;M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-12	.;.;D
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	.;.;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.84
MutPred		0.73		.;Gain of disorder (P = 9e-04);Gain of disorder (P = 9e-04);
MVP		0.92
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.96
gMVP		0.70

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-10204192;