11-101907867-A-G

Variant summary

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

The NM_178127.5(ANGPTL5):c.43T>C(p.Cys15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 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: 6.9e-7 (0 hom.)
• Consequence: ANGPTL5 NM_178127.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.708

Genes affected

ANGPTL5 (HGNC:19705): (angiopoietin like 5) Predicted to be active in collagen-containing extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPTL5	NM_178127.5	c.43T>C	p.Cys15Arg	missense_variant	2/9	ENST00000334289.7
ANGPTL5	XM_011542735.4	c.43T>C	p.Cys15Arg	missense_variant	2/7
ANGPTL5	XM_017017466.3	c.43T>C	p.Cys15Arg	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANGPTL5	ENST00000334289.7	c.43T>C	p.Cys15Arg	missense_variant	2/9	1	NM_178127.5	P1
ANGPTL5	ENST00000534527.1	c.43T>C	p.Cys15Arg	missense_variant	1/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458764 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725908

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.43T>C (p.C15R) alteration is located in exon 2 (coding exon 1) of the ANGPTL5 gene. This alteration results from a T to C substitution at nucleotide position 43, causing the cysteine (C) at amino acid position 15 to be replaced by an arginine (R). 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	20
Dann	Benign	0.95
DEOGEN2	Benign	0.0079	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.058
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.41	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.9	M;.
MutationTaster	Benign	0.52	D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.68	N;N
REVEL	Benign	0.13
Sift	Benign	0.031	D;D
Sift4G	Benign	0.077	T;D
Polyphen		0.38	B;.
Vest4		0.37
MutPred		0.49		Loss of sheet (P = 3e-04);Loss of sheet (P = 3e-04);
MVP		0.63
MPC		0.015
ClinPred		0.21	T
GERP RS		4.1
Varity_R		0.27
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.31		Position offset: 4

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: chr11-101778598;