2-177222437-G-T

Variant names:

• chr2-177222437-G-T
• rs2588882
• NM_194247.4:c.*3045G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194247.4(HNRNPA3):​c.*3045G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 152,224 control chromosomes in the GnomAD database, including 63,123 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.91 (63123 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: HNRNPA3 NM_194247.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 15 publications found

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]

NFE2L2 (HGNC:7782): (NFE2 like bZIP transcription factor 2) This gene encodes a transcription factor which is a member of a small family of basic leucine zipper (bZIP) proteins. The encoded transcription factor regulates genes which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to injury and inflammation which includes the production of free radicals. Multiple transcript variants encoding different isoforms have been characterized for this gene. [provided by RefSeq, Sep 2015]

NFE2L2 Gene-Disease associations (from GenCC):

• immunodeficiency, developmental delay, and hypohomocysteinemia

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNRNPA3	NM_194247.4	c.*3045G>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000392524.7	NP_919223.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPA3	ENST00000392524.7	c.*3045G>T		3_prime_UTR_variant	Exon 11 of 11	5	NM_194247.4	ENSP00000376309.2

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138410 AN: 152106 Hom.: 63069 Cov.: 32

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.916

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.910 AC: 138524 AN: 152224 Hom.: 63123 Cov.: 32 AF XY: 0.907 AC XY: 67495 AN XY: 74416

African (AFR) AF: 0.929 AC: 38567 AN: 41528

American (AMR) AF: 0.916 AC: 14017 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3188 AN: 3472

East Asian (EAS) AF: 0.794 AC: 4103 AN: 5168

South Asian (SAS) AF: 0.893 AC: 4314 AN: 4830

European-Finnish (FIN) AF: 0.867 AC: 9183 AN: 10594

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62165 AN: 68022

Other (OTH) AF: 0.917 AC: 1934 AN: 2108

Alfa AF: 0.918 Hom.: 24749

Bravo AF: 0.915

Asia WGS AF: 0.854 AC: 2973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.42
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2588882; hg19: chr2-178087165;