chr11-101895022-T-C

Position:

• chr11-101895022-T-C

Variant summary

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

The NM_178127.5(ANGPTL5):​c.704A>G​(p.Asn235Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.31

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	Protein	UniProt
ANGPTL5	NM_178127.5	c.704A>G	p.Asn235Ser	missense_variant	8/9	ENST00000334289.7	NP_835228.2
ANGPTL5	XM_011542735.4	c.509A>G	p.Asn170Ser	missense_variant	6/7		XP_011541037.1
ANGPTL5	XM_017017466.3	c.284A>G	p.Asn95Ser	missense_variant	4/5		XP_016872955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPTL5	ENST00000334289.7	c.704A>G	p.Asn235Ser	missense_variant	8/9	1	NM_178127.5	ENSP00000335255	P1
ANGPTL5	ENST00000534527.1	c.509A>G	p.Asn170Ser	missense_variant	5/5	3		ENSP00000433562

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

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

Dec 14, 2023

The c.704A>G (p.N235S) alteration is located in exon 8 (coding exon 7) of the ANGPTL5 gene. This alteration results from a A to G substitution at nucleotide position 704, causing the asparagine (N) at amino acid position 235 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	Benign	0.10
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Benign	0.72	N;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Uncertain	0.49
Sift	Benign	0.24	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.96	D;.
Vest4		0.81
MutPred		0.51		Loss of helix (P = 0.1299);.;
MVP		0.87
MPC		0.081
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.35
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1366809371; hg19: chr11-101765753;