rs760282480

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005968.5(HNRNPM):c.106C>G(p.Pro36Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000638 in 1,410,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P36S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

HNRNPM
NM_005968.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.282

Publications

0 publications found

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:

ENSG00000279827 (HGNC:):

ENSG00000279827 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011064261).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005968.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HNRNPM	NM_005968.5	MANE Select	c.106C>G	p.Pro36Ala	missense	Exon 1 of 16	NP_005959.2
HNRNPM	NM_031203.4		c.106C>G	p.Pro36Ala	missense	Exon 1 of 17	NP_112480.2	P52272-2
HNRNPM	NM_001297418.2		c.-202C>G		5_prime_UTR	Exon 1 of 14	NP_001284347.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HNRNPM	ENST00000325495.9	TSL:1 MANE Select	c.106C>G	p.Pro36Ala	missense	Exon 1 of 16	ENSP00000325376.2	P52272-1
HNRNPM	ENST00000348943.7	TSL:1	c.106C>G	p.Pro36Ala	missense	Exon 1 of 17	ENSP00000325732.2	P52272-2
HNRNPM	ENST00000940928.1		c.106C>G	p.Pro36Ala	missense	Exon 1 of 15	ENSP00000610987.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000536

AC:

AN:

55942

AF XY:

0.0000325

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000556

AC:

AN:

1258446

Hom.:

Cov.:

AF XY:

0.00000651

AC XY:

AN XY:

614884

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24782

American (AMR)

AF:

0.000184

AC:

AN:

10874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19520

East Asian (EAS)

AF:

0.00

AC:

AN:

28662

South Asian (SAS)

AF:

0.0000170

AC:

AN:

58924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5086

European-Non Finnish (NFE)

AF:

9.87e-7

AC:

AN:

1012984

Other (OTH)

AF:

0.0000587

AC:

AN:

51120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151894

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41362

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67910

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000273

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.080

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.54

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.071

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.46

PhyloP100

0.28

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.16

REVEL

Benign

0.061

Sift

Benign

0.64

Sift4G

Benign

0.80

Polyphen

0.0010

Vest4

0.21

MutPred

0.17

Loss of glycosylation at P36 (P = 0.0621)

MVP

0.44

MPC

0.54

ClinPred

0.022

GERP RS

3.9

PromoterAI

-0.065

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.078

gMVP

0.35

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over