2-177216938-A-G

Position:

• chr2-177216938-A-G

Variant summary

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

The NM_194247.4(HNRNPA3):​c.818A>G​(p.Asp273Gly) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HNRNPA3 NM_194247.4 missense, splice_region
• Scores: Splicing: ADA: 0.003183
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.53

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18558335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPA3	NM_194247.4	c.818A>G	p.Asp273Gly	missense_variant, splice_region_variant	7/11	ENST00000392524.7	NP_919223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPA3	ENST00000392524.7	c.818A>G	p.Asp273Gly	missense_variant, splice_region_variant	7/11	5	NM_194247.4	ENSP00000376309.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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

Jul 05, 2024

The c.818A>G (p.D273G) alteration is located in exon 7 (coding exon 7) of the HNRNPA3 gene. This alteration results from a A to G substitution at nucleotide position 818, causing the aspartic acid (D) at amino acid position 273 to be replaced by a glycine (G). 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	0.36
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	27
DANN	Benign	0.93
DEOGEN2	Benign	0.031	T;.;T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.58
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.79	.;T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.94	L;.;L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.15	N;N;N;N
REVEL	Uncertain	0.31
Sift	Benign	0.15	T;T;T;T
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.075	B;.;B;.
Vest4		0.54
MutPred		0.36		Gain of catalytic residue at G271 (P = 0.236);.;Gain of catalytic residue at G271 (P = 0.236);.;
MVP		0.93
MPC		1.2
ClinPred		0.38	T
GERP RS		3.0
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.1
Varity_R		0.14
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0032
dbscSNV1_RF	Benign	0.16
SpliceAI score (max)		0.060		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: chr2-178081666;