rs2277987

Positions:

• chr19-8487389-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005968.5(HNRNPM):​c.2029+314A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 347,248 control chromosomes in the GnomAD database, including 13,724 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 0.23 (4961 hom., cov: 33)
  • Exomes 𝑓: 0.29 (8763 hom.)
• Consequence: HNRNPM NM_005968.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

Genes affected

HNRNPM (HGNC:5046): (heterogeneous nuclear ribonucleoprotein M) This gene belongs to the 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 three repeats of quasi-RRM domains that bind to RNAs. This protein also constitutes a monomer of the N-acetylglucosamine-specific receptor which is postulated to trigger selective recycling of immature GlcNAc-bearing thyroglobulin molecules. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNRNPM	NM_005968.5	c.2029+314A>G		intron_variant		ENST00000325495.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNRNPM	ENST00000325495.9	c.2029+314A>G		intron_variant		1	NM_005968.5	P4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34813 AN: 152090 Hom.: 4967 Cov.: 33

Gnomad AFR AF: 0.0650

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.286 AC: 55849 AN: 195040 Hom.: 8763 Cov.: 0 AF XY: 0.287 AC XY: 30371 AN XY: 105722

Gnomad4 AFR exome AF: 0.0553

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.489

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.229 AC: 34810 AN: 152208 Hom.: 4961 Cov.: 33 AF XY: 0.226 AC XY: 16839 AN XY: 74422

Gnomad4 AFR AF: 0.0648

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.237

Alfa AF: 0.278 Hom.: 3155

Bravo AF: 0.219

Asia WGS AF: 0.361 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.58

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

LitVar

Other links and lift over

dbSNP: rs2277987; hg19: chr19-8552273;