1-23310548-GG-AA

Variant names:

• chr1-23310548-GG-AA
• NM_005826.5:c.1807_1808delCCinsTT
• HNRNPR p.Pro603Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_005826.5(HNRNPR):​c.1807_1808delCCinsTT​(p.Pro603Leu) variant causes a missense 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HNRNPR NM_005826.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.94
• Publications: 0 publications found

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]

HNRNPR Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005826.5. 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
	HNRNPR	NM_005826.5	MANE Select	c.1807_1808delCCinsTT	p.Pro603Leu	missense	N/A	NP_005817.1	O43390-1
	HNRNPR	NM_001102398.3		c.1816_1817delCCinsTT	p.Pro606Leu	missense	N/A	NP_001095868.1	O43390-2
	HNRNPR	NM_001438564.1		c.1807_1808delCCinsTT	p.Pro603Leu	missense	N/A	NP_001425493.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPR	ENST00000302271.11	TSL:1 MANE Select	c.1807_1808delCCinsTT	p.Pro603Leu	missense	N/A	ENSP00000304405.6	O43390-1
	HNRNPR	ENST00000374616.7	TSL:1	c.1816_1817delCCinsTT	p.Pro606Leu	missense	N/A	ENSP00000363745.3	O43390-2
	HNRNPR	ENST00000478691.5	TSL:1	c.1513_1514delCCinsTT	p.Pro505Leu	missense	N/A	ENSP00000474437.1	O43390-4

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-23637041;