2-177217714-A-C

Variant names:

• chr2-177217714-A-C
• NM_194247.4:c.830A>C

Variant summary

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

The NM_194247.4(HNRNPA3):​c.830A>C​(p.Tyr277Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,448 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HNRNPA3 NM_194247.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.28

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]

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
HNRNPA3	NM_194247.4	c.830A>C	p.Tyr277Ser	missense_variant	Exon 8 of 11	ENST00000392524.7	NP_919223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPA3	ENST00000392524.7	c.830A>C	p.Tyr277Ser	missense_variant	Exon 8 of 11	5	NM_194247.4	ENSP00000376309.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460448 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726562

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.830A>C (p.Y277S) alteration is located in exon 8 (coding exon 8) of the HNRNPA3 gene. This alteration results from a A to C substitution at nucleotide position 830, causing the tyrosine (Y) at amino acid position 277 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	0.29
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.19	T;.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.12	.;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Uncertain	2.8	M;.;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.034	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.70
MutPred		0.33		Gain of glycosylation at Y277 (P = 0.0012);.;Gain of glycosylation at Y277 (P = 0.0012);
MVP		0.89
MPC		1.3
ClinPred		0.96	D
GERP RS		4.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.44
gMVP		0.98

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: chr2-178082442;