19-8487389-A-G

Variant names:

• chr19-8487389-A-G
• rs2277987
• NM_005968.5:c.2029+314A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HNRNPM	NM_005968.5	c.2029+314A>G		intron_variant	Intron 15 of 15	ENST00000325495.9	NP_005959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNRNPM	ENST00000325495.9	c.2029+314A>G		intron_variant	Intron 15 of 15	1	NM_005968.5	ENSP00000325376.2

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

African (AFR) AF: 0.0553 AC: 316 AN: 5710

American (AMR) AF: 0.185 AC: 1351 AN: 7312

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 1192 AN: 5232

East Asian (EAS) AF: 0.489 AC: 4365 AN: 8922

South Asian (SAS) AF: 0.275 AC: 9135 AN: 33160

European-Finnish (FIN) AF: 0.244 AC: 2349 AN: 9644

Middle Eastern (MID) AF: 0.261 AC: 194 AN: 742

European-Non Finnish (NFE) AF: 0.300 AC: 34215 AN: 114094

Other (OTH) AF: 0.267 AC: 2732 AN: 10224

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

African (AFR) AF: 0.0648 AC: 2691 AN: 41558

American (AMR) AF: 0.201 AC: 3080 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 769 AN: 3470

East Asian (EAS) AF: 0.502 AC: 2599 AN: 5174

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4824

European-Finnish (FIN) AF: 0.238 AC: 2517 AN: 10594

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20754 AN: 67974

Other (OTH) AF: 0.237 AC: 502 AN: 2116

Alfa AF: 0.279 Hom.: 3468

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
PhyloP100		-0.047
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2277987; hg19: chr19-8552273;