5-137753163-C-T

Variant names:

• chr5-137753163-C-T
• NM_006805.4:c.904G>A

Variant summary

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

The NM_006805.4(HNRNPA0):​c.904G>A​(p.Gly302Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HNRNPA0 NM_006805.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08

Genes affected

HNRNPA0 (HGNC:5030): (heterogeneous nuclear ribonucleoprotein A0) This gene belongs to the A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two repeats of quasi-RRM domains that bind RNAs, followed by a glycine-rich C-terminus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPA0	NM_006805.4	c.904G>A	p.Gly302Ser	missense_variant	Exon 1 of 1	ENST00000314940.7	NP_006796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPA0	ENST00000314940.7	c.904G>A	p.Gly302Ser	missense_variant	Exon 1 of 1	6	NM_006805.4	ENSP00000316042.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.904G>A (p.G302S) alteration is located in exon 1 (coding exon 1) of the HNRNPA0 gene. This alteration results from a G to A substitution at nucleotide position 904, causing the glycine (G) at amino acid position 302 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	0.072
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.061
Eigen_PC	Benign	0.073
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.62	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.91	N
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.51
MutPred		0.27		Gain of phosphorylation at G302 (P = 0.0051);
MVP		0.81
MPC		1.4
ClinPred		0.78	D
GERP RS		3.3
Varity_R		0.69
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-137088852;