Genetic Variant NM_005968.5:c.7G>T (chr19-8445005-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005968.5(HNRNPM):c.7G>T(p.Ala3Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000158 in 1,269,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

HNRNPM
NM_005968.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.44

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23129067).

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.7G>T	p.Ala3Ser	missense	Exon 1 of 16	NP_005959.2
HNRNPM	NM_031203.4		c.7G>T	p.Ala3Ser	missense	Exon 1 of 17	NP_112480.2	P52272-2
HNRNPM	NM_001297418.2		c.-301G>T		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.7G>T	p.Ala3Ser	missense	Exon 1 of 16	ENSP00000325376.2	P52272-1
HNRNPM	ENST00000348943.7	TSL:1	c.7G>T	p.Ala3Ser	missense	Exon 1 of 17	ENSP00000325732.2	P52272-2
HNRNPM	ENST00000940928.1		c.7G>T	p.Ala3Ser	missense	Exon 1 of 15	ENSP00000610987.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000158

AC:

AN:

1269076

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

619792

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25212

American (AMR)

AF:

0.00

AC:

AN:

13216

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18256

East Asian (EAS)

AF:

0.00

AC:

AN:

29526

South Asian (SAS)

AF:

0.00

AC:

AN:

58006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46666

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4826

European-Non Finnish (NFE)

AF:

0.00000196

AC:

AN:

1021606

Other (OTH)

AF:

0.00

AC:

AN:

51762

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.072

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

4.4

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.38

REVEL

Benign

0.092

Sift

Pathogenic

0.0

Sift4G

Benign

0.088

Polyphen

0.76

Vest4

0.48

MutPred

0.23

Gain of glycosylation at A3 (P = 0.0049)

MVP

0.41

MPC

0.51

ClinPred

0.76

GERP RS

5.2

PromoterAI

-0.10

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.51

gMVP

0.42

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over