rs747301226

Variant names:

• chr1-244862498-ATCT-A
• rs747301226
• NM_031844.3:c.837_839delAGA

Your query was ambiguous. Multiple possible variants found:

• chr1-244862498-ATCT-A
• chr1-244862498-ATCT-ATCTTCT

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_031844.3(HNRNPU):​c.837_839delAGA​(p.Glu279del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,742 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: 0.0000041 (0 hom.)
• Consequence: HNRNPU NM_031844.3 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 8.00
• Publications: 4 publications found

Genes affected

HNRNPU (HGNC:5048): (heterogeneous nuclear ribonucleoprotein U) This gene encodes a member of a family of proteins that bind nucleic acids and function in the formation of ribonucleoprotein complexes in the nucleus with heterogeneous nuclear RNA (hnRNA). The encoded protein has affinity for both RNA and DNA, and binds scaffold-attached region (SAR) DNA. Mutations in this gene have been associated with epileptic encephalopathy, early infantile, 54. A pseudogene of this gene has been identified on chromosome 14. [provided by RefSeq, Jun 2017]

HNRNPU Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 54

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_031844.3. Strenght limited to Supporting due to length of the change: 1aa.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031844.3. 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
	HNRNPU	NM_031844.3	MANE Select	c.837_839delAGA	p.Glu279del	disruptive_inframe_deletion	Exon 3 of 14	NP_114032.2	Q00839-1
	HNRNPU	NM_004501.3		c.780_782delAGA	p.Glu260del	disruptive_inframe_deletion	Exon 3 of 14	NP_004492.2	Q00839-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPU	ENST00000640218.2	TSL:1 MANE Select	c.837_839delAGA	p.Glu279del	disruptive_inframe_deletion	Exon 3 of 14	ENSP00000491215.1	Q00839-1
	HNRNPU	ENST00000444376.7	TSL:1	c.780_782delAGA	p.Glu260del	disruptive_inframe_deletion	Exon 3 of 14	ENSP00000393151.2	Q00839-2
	HNRNPU	ENST00000919769.1		c.837_839delAGA	p.Glu279del	disruptive_inframe_deletion	Exon 3 of 15	ENSP00000589828.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000795 AC: 2 AN: 251462 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461742 Hom.: 0 AF XY: 0.00000688 AC XY: 5 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111890

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Developmental and epileptic encephalopathy, 54 (2)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs747301226; hg19: chr1-245025800; COSMIC: COSV51689865; COSMIC: COSV51689865;