Variant 3-49030569-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_198880.3(QRICH1):c.2214C>G(p.Ile738Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

QRICH1
NM_198880.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

Variant links:

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 links:

ENSG00000290315 (HGNC:):

ENSG00000290315 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), QRICH1. . Gene score misZ 3.7104 (greater than the threshold 3.09). Trascript score misZ 3.7807 (greater than threshold 3.09). GenCC has associacion of gene with syndromic intellectual disability, schizophrenia, Ververi-Brady syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.22888023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
QRICH1	NM_198880.3 linkuse as main transcript	c.2214C>G	p.Ile738Met	missense_variant	10/10	ENST00000395443.7	NP_942581.1	Q2TAL8A1L3Z9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
QRICH1	ENST00000395443.7 linkuse as main transcript	c.2214C>G	p.Ile738Met	missense_variant	10/10	1	NM_198880.3	ENSP00000378830.2		Q2TAL8
ENSG00000290315	ENST00000703936.1 linkuse as main transcript	c.2138+1614C>G		intron_variant				ENSP00000515567.1		A0A994J749

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250700

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461134

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726830

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ververi-Brady syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn

Dec 09, 2021

PP2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

0.025

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.85

.;.;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.035

N;N;N

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.80

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.36

T;T;T

Polyphen

0.45

B;B;B

Vest4

0.24

MutPred

0.42

Gain of catalytic residue at I738 (P = 0.0046);Gain of catalytic residue at I738 (P = 0.0046);Gain of catalytic residue at I738 (P = 0.0046);

MVP

0.50

MPC

1.3

ClinPred

0.41

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.53

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

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