19-41276273-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2 BP4 BS2

The NM_007040.6(HNRNPUL1):c.761G>C(p.Arg254Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000754 in 1,459,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: HNRNPUL1 NM_007040.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53

Genes affected

HNRNPUL1 (HGNC:17011): (heterogeneous nuclear ribonucleoprotein U like 1) This gene encodes a nuclear RNA-binding protein of the heterogeneous nuclear ribonucleoprotein (hnRNP) family. This protein binds specifically to adenovirus early-1B-55kDa oncoprotein. It may play an important role in nucleocytoplasmic RNA transport, and its function is modulated by early-1B-55kDa in adenovirus-infected cells. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PP2: Missense variant where missense usually causes diseases, HNRNPUL1
• BP4: Computational evidence support a benign effect (MetaRNN=0.2741974).
• BS2: High AC in GnomAdExome at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPUL1	NM_007040.6	c.761G>C	p.Arg254Thr	missense_variant	5/15	ENST00000392006.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPUL1	ENST00000392006.8	c.761G>C	p.Arg254Thr	missense_variant	5/15	1	NM_007040.6	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000518 AC: 13 AN: 251004 Hom.: 0 AF XY: 0.0000295 AC XY: 4 AN XY: 135658

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1459338 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 725372

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000246

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.761G>C (p.R254T) alteration is located in exon 5 (coding exon 5) of the HNRNPUL1 gene. This alteration results from a G to C substitution at nucleotide position 761, causing the arginine (R) at amino acid position 254 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.18
Cadd	Uncertain	25
Dann	Benign	0.97
DEOGEN2	Benign	0.033	T;.;.;T;T;.;.;T;.;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T;.;T;D;T;D;T;D;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.27	T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.25	T
MutationTaster	Benign	0.95	D;D;D;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.7	D;.;.;.;D;D;.;.;.;D
REVEL	Benign	0.25
Sift	Benign	0.15	T;.;.;.;T;T;.;.;.;T
Sift4G	Uncertain	0.0040	D;D;D;D;D;D;D;D;D;D
Polyphen		0.067, 0.034, 0.95, 0.34, 0.017	.;B;.;.;B;P;B;.;B;B
Vest4		0.53
MutPred		0.45		.;.;.;.;Loss of methylation at R254 (P = 0.0261);.;Loss of methylation at R254 (P = 0.0261);.;.;.;
MVP		0.49
MPC		1.0
ClinPred		0.13	T
GERP RS		6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.38
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs769253732; hg19: chr19-41782178;