Variant chr11-57614435-G-GTGT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4_SupportingPP5

The NM_000062.3(SERPING1):c.1357_1358insTGT(p.Gly453delinsValTrp) variant causes a disruptive inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

SERPING1
NM_000062.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.14

Variant links:

Genes affected

SERPING1 (HGNC:1228): (serpin family G member 1) This gene encodes a highly glycosylated plasma protein involved in the regulation of the complement cascade. Its encoded protein, C1 inhibitor, inhibits activated C1r and C1s of the first complement component and thus regulates complement activation. It is synthesized in the liver, and its deficiency is associated with hereditary angioneurotic oedema (HANE). Alternative splicing results in multiple transcript variants encoding the same isoform. [provided by RefSeq, May 2020]

SERPING1 links:

SERPING1 (HGNC:):

SERPING1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM1

In a strand (size 2) in uniprot entity IC1_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_000062.3

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_000062.3. Strenght limited to Supporting due to length of the change: 1aa.

PP5

Variant 11-57614435-G-GTGT is Pathogenic according to our data. Variant chr11-57614435-G-GTGT is described in ClinVar as [Pathogenic]. Clinvar id is 3954.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SERPING1	NM_000062.3 linkuse as main transcript	c.1357_1358insTGT	p.Gly453delinsValTrp	disruptive_inframe_insertion	8/8	ENST00000278407.9	NP_000053.2	P05155-1E9KL26
SERPING1	NM_001032295.2 linkuse as main transcript	c.1357_1358insTGT	p.Gly453delinsValTrp	disruptive_inframe_insertion	7/7		NP_001027466.1	P05155-1E9KL26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SERPING1	ENST00000278407.9 linkuse as main transcript	c.1357_1358insTGT	p.Gly453delinsValTrp	disruptive_inframe_insertion	8/8	1	NM_000062.3	ENSP00000278407.4		P05155-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hereditary C1 esterase inhibitor deficiency - dysfunctional factor

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 1993

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over