rs41322046

Variant names:

• chr9-127825812-C-G
• NM_001114753.3:c.572G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-127825812-C-G
• chr9-127825812-C-T

Variant summary

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

The NM_001114753.3(ENG):​c.572G>C​(p.Gly191Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G191D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENG NM_001114753.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

Genes affected

ENG (HGNC:3349): (endoglin) This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds to the beta1 and beta3 peptides with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in preeclampsia and several types of cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]

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 rank	MANE	Protein	UniProt
ENG	NM_001114753.3	c.572G>C	p.Gly191Ala	missense_variant	Exon 5 of 15	ENST00000373203.9	NP_001108225.1
ENG	NM_000118.4	c.572G>C	p.Gly191Ala	missense_variant	Exon 5 of 14		NP_000109.1
ENG	NM_001278138.2	c.26G>C	p.Gly9Ala	missense_variant	Exon 5 of 15		NP_001265067.1
ENG	NM_001406715.1	c.572G>C	p.Gly191Ala	missense_variant	Exon 5 of 8		NP_001393644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENG	ENST00000373203.9	c.572G>C	p.Gly191Ala	missense_variant	Exon 5 of 15	1	NM_001114753.3	ENSP00000362299.4
ENG	ENST00000344849.4	c.572G>C	p.Gly191Ala	missense_variant	Exon 5 of 14	1		ENSP00000341917.3
ENG	ENST00000480266.6	c.26G>C	p.Gly9Ala	missense_variant	Exon 5 of 15	2		ENSP00000479015.1
ENG	ENST00000462196.1	n.472G>C		non_coding_transcript_exon_variant	Exon 4 of 4	3		ENSP00000519251.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T;T;.
Eigen	Benign	-0.026
Eigen_PC	Benign	0.0083
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M;.;M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	N;.;N
REVEL	Benign	0.14
Sift	Benign	0.45	T;.;T
Sift4G	Benign	0.29	T;D;T
Polyphen		0.41	B;.;.
Vest4		0.31
MutPred		0.67		Gain of helix (P = 0.0082);.;Gain of helix (P = 0.0082);
MVP		0.65
MPC		0.38
ClinPred		0.48	T
GERP RS		4.4
Varity_R		0.23
gMVP		0.54

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130588091;