rs3210983

Variant names:

• chr19-8373879-C-T
• rs3210983
• NM_139314.3:c.1214C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_139314.3(ANGPTL4):​c.1214C>T​(p.Ala405Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANGPTL4 NM_139314.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 0 publications found

Genes affected

ANGPTL4 (HGNC:16039): (angiopoietin like 4) This gene encodes a glycosylated, secreted protein containing a C-terminal fibrinogen domain. The encoded protein is induced by peroxisome proliferation activators and functions as a serum hormone that regulates glucose homeostasis, lipid metabolism, and insulin sensitivity. This protein can also act as an apoptosis survival factor for vascular endothelial cells and can prevent metastasis by inhibiting vascular growth and tumor cell invasion. The C-terminal domain may be proteolytically-cleaved from the full-length secreted protein. Decreased expression of this gene has been associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. This gene was previously referred to as ANGPTL2 but has been renamed ANGPTL4. [provided by RefSeq, Sep 2013]

RAB11B-AS1 (HGNC:44178): (RAB11B antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18585771).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139314.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL4	NM_139314.3	MANE Select	c.1214C>T	p.Ala405Val	missense	Exon 7 of 7	NP_647475.1	Q9BY76-1
	ANGPTL4	NM_001039667.3		c.1100C>T	p.Ala367Val	missense	Exon 6 of 6	NP_001034756.1	Q9BY76-2
	ANGPTL4	NR_104213.2		n.597-314C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL4	ENST00000301455.7	TSL:1 MANE Select	c.1214C>T	p.Ala405Val	missense	Exon 7 of 7	ENSP00000301455.1	Q9BY76-1
	ANGPTL4	ENST00000593998.5	TSL:1	n.1214C>T		non_coding_transcript_exon	Exon 7 of 8	ENSP00000472551.1	Q9BY76-1
	ANGPTL4	ENST00000955923.1		c.1214C>T	p.Ala405Val	missense	Exon 8 of 8	ENSP00000625982.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460956 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726772

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5586

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	M
PhyloP100		1.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.092
Sift	Uncertain	0.014	D
Sift4G	Benign	0.080	T
Polyphen		0.93	P
Vest4		0.20
MutPred		0.19		Loss of relative solvent accessibility (P = 0.0186)
MVP		0.80
MPC		0.53
ClinPred		0.38	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.49
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3210983; hg19: chr19-8438763;