11-101907849-C-T

Position:

• chr11-101907849-C-T

Variant summary

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

The NM_178127.5(ANGPTL5):​c.61G>A​(p.Glu21Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: ANGPTL5 NM_178127.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.575

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26046827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPTL5	NM_178127.5	c.61G>A	p.Glu21Lys	missense_variant	2/9	ENST00000334289.7	NP_835228.2
ANGPTL5	XM_011542735.4	c.61G>A	p.Glu21Lys	missense_variant	2/7		XP_011541037.1
ANGPTL5	XM_017017466.3	c.61G>A	p.Glu21Lys	missense_variant	2/5		XP_016872955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPTL5	ENST00000334289.7	c.61G>A	p.Glu21Lys	missense_variant	2/9	1	NM_178127.5	ENSP00000335255	P1
ANGPTL5	ENST00000534527.1	c.61G>A	p.Glu21Lys	missense_variant	1/5	3		ENSP00000433562

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Jun 03, 2022

The c.61G>A (p.E21K) alteration is located in exon 2 (coding exon 1) of the ANGPTL5 gene. This alteration results from a G to A substitution at nucleotide position 61, causing the glutamic acid (E) at amino acid position 21 to be replaced by a lysine (K). 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	Benign	0.075
BayesDel_addAF	Benign	-0.00033	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0041	T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	0.85	N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.090	N;N
REVEL	Benign	0.17
Sift	Benign	0.087	T;D
Sift4G	Benign	0.12	T;D
Polyphen		0.96	P;.
Vest4		0.36
MutPred		0.45		Loss of sheet (P = 3e-04);Loss of sheet (P = 3e-04);
MVP		0.66
MPC		0.012
ClinPred		0.85	D
GERP RS		5.2
Varity_R		0.20
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr11-101778580;