3-49032688-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_198880.3(QRICH1):c.1981C>T(p.Pro661Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: QRICH1 NM_198880.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.92

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, QRICH1
• BP4: Computational evidence support a benign effect (MetaRNN=0.23327127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
QRICH1	NM_198880.3	c.1981C>T	p.Pro661Ser	missense_variant	8/10	ENST00000395443.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
QRICH1	ENST00000395443.7	c.1981C>T	p.Pro661Ser	missense_variant	8/10	1	NM_198880.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250578 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135488

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460850 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000450

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ververi-Brady syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Jan 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.20
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.028	T;T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.90	L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.79	N;N;N
REVEL	Benign	0.087
Sift	Benign	0.056	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.79	P;P;P
Vest4		0.33
MutPred		0.30		Gain of phosphorylation at P661 (P = 0.0262);Gain of phosphorylation at P661 (P = 0.0262);Gain of phosphorylation at P661 (P = 0.0262);
MVP		0.082
MPC		1.3
ClinPred		0.67	D
GERP RS		5.5
Varity_R		0.095
gMVP		0.60

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

Other links and lift over

dbSNP: rs1314981903; hg19: chr3-49070121;