14-76790711-C-G

Variant names:

• chr14-76790711-C-G
• rs774086155
• NM_015305.4:c.1752G>C

Variant summary

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

The NM_015305.4(ANGEL1):​c.1752G>C​(p.Gln584His) 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. 14/22 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: ANGEL1 NM_015305.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74
• Publications: 0 publications found

Genes affected

ANGEL1 (HGNC:19961): (angel homolog 1) Enables eukaryotic initiation factor 4E binding activity and protein domain specific binding activity. Predicted to be involved in RNA phosphodiester bond hydrolysis, exonucleolytic. Located in several cellular components, including cis-Golgi network; endoplasmic reticulum; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286437 (HGNC:):

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=0.22917855).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015305.4. 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
	ANGEL1	NM_015305.4	MANE Select	c.1752G>C	p.Gln584His	missense	Exon 9 of 10	NP_056120.2	Q9UNK9
	ANGEL1	NM_001370746.1		c.1911G>C	p.Gln637His	missense	Exon 11 of 12	NP_001357675.1
	ANGEL1	NM_001370747.1		c.1911G>C	p.Gln637His	missense	Exon 11 of 12	NP_001357676.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGEL1	ENST00000251089.8	TSL:1 MANE Select	c.1752G>C	p.Gln584His	missense	Exon 9 of 10	ENSP00000251089.3	Q9UNK9
	ANGEL1	ENST00000851327.1		c.1911G>C	p.Gln637His	missense	Exon 11 of 12	ENSP00000521386.1
	ANGEL1	ENST00000557497.2	TSL:2	c.1791G>C	p.Gln597His	missense	Exon 10 of 11	ENSP00000498076.2	A0A3B3IU54

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.089	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.7
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.055
Sift	Benign	0.036	D
Sift4G	Benign	0.092	T
Polyphen		0.49	P
Vest4		0.31
MutPred		0.37		Gain of catalytic residue at L582 (P = 0.0011)
MVP		0.60
MPC		0.13
ClinPred		0.54	D
GERP RS		4.9
Varity_R		0.053
gMVP		0.53
Mutation Taster		=88/12	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: rs774086155; hg19: chr14-77257054;