rs1553747119

Variant names:

• chr3-49076879-GC-AA
• rs1553747119
• NM_198880.3:c.138_139delGCinsTT

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_198880.3(QRICH1):​c.138_139delGCinsTT​(p.GlnGln46*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: QRICH1 NM_198880.3 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 9.60
• Publications: 1 publications found

Genes affected

QRICH1 (HGNC:24713): (glutamine rich 1) Enables DNA binding activity. Involved in several processes, including PERK-mediated unfolded protein response; intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; and positive regulation of transcription, DNA-templated. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

QRICH1 Gene-Disease associations (from GenCC):

• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Ververi-Brady syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000290315 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 3-49076879-GC-AA is Pathogenic according to our data. Variant chr3-49076879-GC-AA is described in ClinVar as Pathogenic. ClinVar VariationId is 523659.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198880.3. 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
	QRICH1	NM_198880.3	MANE Select	c.138_139delGCinsTT	p.GlnGln46*	stop_gained	N/A	NP_942581.1	A1L3Z9
	QRICH1	NM_001320580.2		c.138_139delGCinsTT	p.GlnGln46*	stop_gained	N/A	NP_001307509.1	A1L3Z9
	QRICH1	NM_001320581.2		c.138_139delGCinsTT	p.GlnGln46*	stop_gained	N/A	NP_001307510.1	Q2TAL8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QRICH1	ENST00000395443.7	TSL:1 MANE Select	c.138_139delGCinsTT	p.GlnGln46*	stop_gained	N/A	ENSP00000378830.2	Q2TAL8
	ENSG00000290315	ENST00000703936.1		c.138_139delGCinsTT	p.GlnGln46*	stop_gained	N/A	ENSP00000515567.1	A0A994J749
	QRICH1	ENST00000357496.6	TSL:2	c.138_139delGCinsTT	p.GlnGln46*	stop_gained	N/A	ENSP00000350094.2	Q2TAL8

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Ververi-Brady syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6
Mutation Taster		=1/199	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs1553747119; hg19: chr3-49114312;