1-23313672-T-A

Position:

• chr1-23313672-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005826.5(HNRNPR):​c.1048A>T​(p.Thr350Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HNRNPR NM_005826.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13101313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPR	NM_005826.5	c.1048A>T	p.Thr350Ser	missense_variant	9/11	ENST00000302271.11	NP_005817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPR	ENST00000302271.11	c.1048A>T	p.Thr350Ser	missense_variant	9/11	1	NM_005826.5	ENSP00000304405.6
HNRNPR	ENST00000374616.7	c.1057A>T	p.Thr353Ser	missense_variant	9/11	1		ENSP00000363745.3
HNRNPR	ENST00000478691.5	c.754A>T	p.Thr252Ser	missense_variant	8/10	1		ENSP00000474437.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.1057A>T (p.T353S) alteration is located in exon 9 (coding exon 8) of the HNRNPR gene. This alteration results from a A to T substitution at nucleotide position 1057, causing the threonine (T) at amino acid position 353 to be replaced by a serine (S). 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	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.084	.;.;T;T;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.13	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.41	.;.;N;N;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.050	.;N;N;N;.;N
REVEL	Benign	0.071
Sift	Benign	0.72	.;T;T;T;.;T
Sift4G	Benign	0.56	T;T;T;T;T;T
Polyphen		0.059, 0.091, 0.21	.;B;B;B;B;.
Vest4		0.17
MutPred		0.36		.;.;Gain of disorder (P = 0.0824);Gain of disorder (P = 0.0824);.;.;
MVP		0.39
MPC		0.58
ClinPred		0.79	D
GERP RS		6.0
Varity_R		0.063
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-23640165;