rs1553578312

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_005199.5(CHRNG):​c.1210C>T​(p.Gln404Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

CHRNG
NM_005199.5 stop_gained

Scores

2
2
3

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.34
Variant links:
Genes affected
CHRNG (HGNC:1967): (cholinergic receptor nicotinic gamma subunit) The mammalian muscle-type acetylcholine receptor is a transmembrane pentameric glycoprotein with two alpha subunits, one beta, one delta, and one epsilon (in adult skeletal muscle) or gamma (in fetal and denervated muscle) subunit. This gene, which encodes the gamma subunit, is expressed prior to the thirty-third week of gestation in humans. The gamma subunit of the acetylcholine receptor plays a role in neuromuscular organogenesis and ligand binding and disruption of gamma subunit expression prevents the correct localization of the receptor in cell membranes. Mutations in this gene cause Escobar syndrome and a lethal form of multiple pterygium syndrome. Muscle-type acetylcholine receptor is the major antigen in the autoimmune disease myasthenia gravis.[provided by RefSeq, Sep 2009]
TIGD1 (HGNC:14523): (tigger transposable element derived 1) The protein encoded by this gene belongs to the tigger subfamily of the pogo superfamily of DNA-mediated transposons in humans. These proteins are related to DNA transposons found in fungi and nematodes, and more distantly to the Tc1 and mariner transposases. They are also very similar to the major mammalian centromere protein B. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-232544541-C-T is Pathogenic according to our data. Variant chr2-232544541-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 487641.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-232544541-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CHRNGNM_005199.5 linkuse as main transcriptc.1210C>T p.Gln404Ter stop_gained 10/12 ENST00000651502.1
TIGD1NM_145702.4 linkuse as main transcriptc.*3566G>A 3_prime_UTR_variant 1/1 ENST00000408957.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CHRNGENST00000651502.1 linkuse as main transcriptc.1210C>T p.Gln404Ter stop_gained 10/12 NM_005199.5 P1P07510-1
CHRNGENST00000389492.3 linkuse as main transcriptc.1054C>T p.Gln352Ter stop_gained 9/111 P07510-2
TIGD1ENST00000408957.7 linkuse as main transcriptc.*3566G>A 3_prime_UTR_variant 1/1 NM_145702.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Lethal multiple pterygium syndrome Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingInstitute of Human Genetics, Cologne UniversityDec 20, 2017ACMG Criteria: PVS1, PM2, PP3 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.63
D
BayesDel_noAF
Pathogenic
0.45
CADD
Pathogenic
36
DANN
Uncertain
0.99
Eigen
Uncertain
0.42
Eigen_PC
Benign
0.15
FATHMM_MKL
Benign
0.69
D
MutationTaster
Benign
1.0
A;A;A
Vest4
0.55
GERP RS
1.9

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

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

Other links and lift over

dbSNP: rs1553578312; hg19: chr2-233409251; API