NM_005826.5:c.1874A>G

Variant names:

• chr1-23310482-T-C
• NM_005826.5:c.1874A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005826.5(HNRNPR):​c.1874A>G​(p.Gln625Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HNRNPR NM_005826.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.97

Genes affected

HNRNPR (HGNC:5047): (heterogeneous nuclear ribonucleoprotein R) This gene encodes an RNA-binding protein that is a member of the spliceosome C complex, which functions in pre-mRNA processing and transport. The encoded protein also promotes transcription at the c-fos gene. Alternative splicing results in multiple transcript variants. There are pseudogenes for this gene on chromosomes 4, 11, and 10. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPR	NM_005826.5	c.1874A>G	p.Gln625Arg	missense_variant	Exon 11 of 11	ENST00000302271.11	NP_005817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPR	ENST00000302271.11	c.1874A>G	p.Gln625Arg	missense_variant	Exon 11 of 11	1	NM_005826.5	ENSP00000304405.6
HNRNPR	ENST00000374616.7	c.1883A>G	p.Gln628Arg	missense_variant	Exon 11 of 11	1		ENSP00000363745.3
HNRNPR	ENST00000478691.5	c.1580A>G	p.Gln527Arg	missense_variant	Exon 10 of 10	1		ENSP00000474437.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 13, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	0.97
DEOGEN2	Benign	0.25	.;.;T;T;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.54	D;D;D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	2.0	.;.;M;M;.;.
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.4	.;N;N;N;.;N
REVEL	Benign	0.23
Sift	Uncertain	0.010	.;D;D;D;.;D
Sift4G	Uncertain	0.016	D;D;D;D;D;D
Polyphen		0.98, 0.85	.;D;P;P;P;.
Vest4		0.69
MutPred		0.23		.;.;Loss of catalytic residue at Q625 (P = 0.021);Loss of catalytic residue at Q625 (P = 0.021);.;.;
MVP		0.63
MPC		0.64
ClinPred		0.81	D
GERP RS		5.2
Varity_R		0.29
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-23636975;