1-23310926-T-C

Variant names:

• chr1-23310926-T-C
• NM_005826.5:c.1430A>G

Variant summary

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

The NM_005826.5(HNRNPR):​c.1430A>G​(p.Tyr477Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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.1430A>G	p.Tyr477Cys	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.1430A>G	p.Tyr477Cys	missense_variant	Exon 11 of 11	1	NM_005826.5	ENSP00000304405.6
HNRNPR	ENST00000374616.7	c.1439A>G	p.Tyr480Cys	missense_variant	Exon 11 of 11	1		ENSP00000363745.3
HNRNPR	ENST00000478691.5	c.1136A>G	p.Tyr379Cys	missense_variant	Exon 10 of 10	1		ENSP00000474437.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

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

not provided Uncertain:1

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HNRNPR: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.67	.;.;D;D;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.65	D;D;D;D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Pathogenic	2.9	.;.;M;M;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.0	.;D;D;D;.;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.015	.;D;D;D;.;D
Sift4G	Benign	0.085	T;T;T;T;T;T
Polyphen		0.99, 0.98	.;D;D;D;D;.
Vest4		0.66
MutPred		0.40		.;.;Loss of phosphorylation at Y477 (P = 0.0398);Loss of phosphorylation at Y477 (P = 0.0398);.;.;
MVP		0.55
MPC		0.75
ClinPred		0.95	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.81

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: chr1-23637419;