chr1-23313672-T-A

Position:

• chr1-23313672-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The ENST00000302271.11(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 ENST00000302271.11 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), HNRNPR. . Gene score misZ 3.5388 (greater than the threshold 3.09). Trascript score misZ 4.0437 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, syndromic intellectual disability, neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities.
• 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	P3

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;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
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;