1-244858744-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_031844.3(HNRNPU):c.1215G>A(p.Val405Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,571,030 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 7 hom. )

Consequence

HNRNPU
NM_031844.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.70

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-244858744-C-T is Benign according to our data. Variant chr1-244858744-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-244858744-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00163 (249/152322) while in subpopulation NFE AF= 0.0022 (150/68028). AF 95% confidence interval is 0.00192. There are 0 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPU	NM_031844.3 link	c.1215G>A	p.Val405Val	synonymous_variant	Exon 6 of 14	ENST00000640218.2	NP_114032.2	Q00839-1Q96BA7
HNRNPU	NM_004501.3 link	c.1158G>A	p.Val386Val	synonymous_variant	Exon 6 of 14		NP_004492.2	Q00839-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPU	ENST00000640218.2 link	c.1215G>A	p.Val405Val	synonymous_variant	Exon 6 of 14	1	NM_031844.3	ENSP00000491215.1		Q00839-1

Frequencies

GnomAD3 genomes

AF:

0.00164

AC:

249

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00220

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00203

AC:

508

AN:

249906

Hom.:

AF XY:

0.00212

AC XY:

286

AN XY:

135030

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.00187

Gnomad ASJ exome

AF:

0.0114

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000630

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00254

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00240

AC:

3411

AN:

1418708

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

1691

AN XY:

708310

show subpopulations

Gnomad4 AFR exome

AF:

0.000399

Gnomad4 AMR exome

AF:

0.00189

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000483

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00257

Gnomad4 OTH exome

AF:

0.00290

GnomAD4 genome

AF:

0.00163

AC:

249

AN:

152322

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00220

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00250

Hom.:

Bravo

AF:

0.00170

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00344

EpiControl

AF:

0.00457

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HNRNPU: BS1 -

Mar 05, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Inborn genetic diseases

Benign:1

Mar 16, 2016

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Developmental and epileptic encephalopathy, 54

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.43

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.43

Position offset: 3

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over