1-244862463-G-T

Variant names:

• chr1-244862463-G-T
• NM_031844.3:c.875C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031844.3(HNRNPU):​c.875C>A​(p.Thr292Asn) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T292I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: HNRNPU NM_031844.3 missense, splice_region
• Scores: Splicing: ADA: 0.9097
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.05

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3877502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPU	NM_031844.3	c.875C>A	p.Thr292Asn	missense_variant, splice_region_variant	Exon 3 of 14	ENST00000640218.2	NP_114032.2
HNRNPU	NM_004501.3	c.818C>A	p.Thr273Asn	missense_variant, splice_region_variant	Exon 3 of 14		NP_004492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPU	ENST00000640218.2	c.875C>A	p.Thr292Asn	missense_variant, splice_region_variant	Exon 3 of 14	1	NM_031844.3	ENSP00000491215.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418398 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 707488

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: 9.30e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	.;T;T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	2.0	.;M;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.2	N;.;D;.
REVEL	Benign	0.24
Sift	Uncertain	0.022	D;.;T;.
Sift4G	Uncertain	0.059	T;.;.;.
Polyphen		0.34	B;B;.;.
Vest4		0.81
MutPred		0.47		.;Gain of relative solvent accessibility (P = 0.09);.;.;
MVP		0.51
ClinPred		0.89	D
GERP RS		5.4
Varity_R		0.49
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.91
dbscSNV1_RF	Benign	0.65
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: chr1-245025765;