Variant 19-8485716-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005968.5(HNRNPM):c.1288G>A(p.Val430Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,454,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HNRNPM
NM_005968.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

Variant links:

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]

HNRNPM links:

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ACMG classification

Classification made for transcript

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=0.15940276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPM	NM_005968.5 linkuse as main transcript	c.1288G>A	p.Val430Met	missense_variant	14/16	ENST00000325495.9	NP_005959.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPM	ENST00000325495.9 linkuse as main transcript	c.1288G>A	p.Val430Met	missense_variant	14/16	1	NM_005968.5	ENSP00000325376	P4	P52272-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243270

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132374

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454914

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.1288G>A (p.V430M) alteration is located in exon 14 (coding exon 14) of the HNRNPM gene. This alteration results from a G to A substitution at nucleotide position 1288, causing the valine (V) at amino acid position 430 to be replaced by a methionine (M). 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

0.15

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.074

.;T;T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.0059

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.0087

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

.;L;.;.

MutationTaster

Benign

0.97

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.20

N;N;.;.

REVEL

Benign

0.077

Sift

Benign

0.61

T;T;.;.

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.18

B;D;.;.

Vest4

0.21

MutPred

0.17

.;Loss of methylation at R429 (P = 0.1525);Loss of methylation at R429 (P = 0.1525);.;

MVP

0.57

MPC

0.58

ClinPred

0.35

GERP RS

4.7

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.9

Varity_R

0.069

gMVP

0.93

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over