2-177217720-G-T

Position:

• chr2-177217720-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_194247.4(HNRNPA3):​c.836G>T​(p.Gly279Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HNRNPA3 NM_194247.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.82

Genes affected

HNRNPA3 (HGNC:24941): (heterogeneous nuclear ribonucleoprotein A3) Enables RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of catalytic step 2 spliceosome. [provided by Alliance of Genome Resources, Apr 2022]

HNRNPA3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPA3	NM_194247.4	c.836G>T	p.Gly279Val	missense_variant	8/11	ENST00000392524.7	NP_919223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPA3	ENST00000392524.7	c.836G>T	p.Gly279Val	missense_variant	8/11	5	NM_194247.4	ENSP00000376309.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Nov 15, 2024

The c.836G>T (p.G279V) alteration is located in exon 8 (coding exon 8) of the HNRNPA3 gene. This alteration results from a G to T substitution at nucleotide position 836, causing the glycine (G) at amino acid position 279 to be replaced by a valine (V). 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	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Benign	0.31	T;.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.12	.;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Pathogenic	3.0	M;.;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.1	D;D;D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.042	D;D;D
Polyphen		0.89	P;.;P
Vest4		0.81
MutPred		0.34		Gain of sheet (P = 0.0166);.;Gain of sheet (P = 0.0166);
MVP		0.83
MPC		1.1
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.60
gMVP		0.99

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: chr2-178082448;