19-10094807-C-A

Position:

• chr19-10094807-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031917.3(ANGPTL6):​c.714G>T​(p.Met238Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ANGPTL6 NM_031917.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071205854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPTL6	NM_031917.3	c.714G>T	p.Met238Ile	missense_variant	3/6	ENST00000253109.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANGPTL6	ENST00000253109.5	c.714G>T	p.Met238Ile	missense_variant	3/6	1	NM_031917.3	P1
ANGPTL6	ENST00000592641.5	c.714G>T	p.Met238Ile	missense_variant	3/6	1		P1
ANGPTL6	ENST00000589181.5	c.714G>T	p.Met238Ile	missense_variant	2/5	5
ANGPTL6	ENST00000586910.1	n.282G>T		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251448 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135888

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.9
DANN	Benign	0.61
DEOGEN2	Benign	0.0076	T;T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.47	T;.;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.11	.;.;N
REVEL	Benign	0.092
Sift	Benign	0.48	.;.;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.16
MutPred		0.15		Loss of glycosylation at P237 (P = 0.0972);Loss of glycosylation at P237 (P = 0.0972);Loss of glycosylation at P237 (P = 0.0972);
MVP		0.44
ClinPred		0.031	T
GERP RS		2.9
Varity_R		0.062
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1260808165; hg19: chr19-10205483;