Genetic Variant NM_006805.4:c.656G>C (chr5-137753411-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006805.4(HNRNPA0):c.656G>C(p.Ser219Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000501 in 1,397,316 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. 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. S219N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

HNRNPA0
NM_006805.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.49

Publications

0 publications found

Variant links:

Genes affected

HNRNPA0 (HGNC:5030): (heterogeneous nuclear ribonucleoprotein A0) This gene belongs to the A/B 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 two repeats of quasi-RRM domains that bind RNAs, followed by a glycine-rich C-terminus. [provided by RefSeq, Jul 2008]

HNRNPA0 Gene-Disease associations (from GenCC):

Tourette syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

HNRNPA0 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34359324).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006805.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPA0	NM_006805.4	MANE Select	c.656G>C	p.Ser219Thr	missense	Exon 1 of 1	NP_006796.1	Q13151

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNRNPA0	ENST00000314940.7	TSL:6 MANE Select	c.656G>C	p.Ser219Thr	missense	Exon 1 of 1	ENSP00000316042.4	Q13151
	HNRNPA0	ENST00000705031.1		c.707G>C	p.Ser236Thr	missense	Exon 1 of 1	ENSP00000516066.1	A0ABB0MN55

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000678

AC:

AN:

147506

AF XY:

0.0000126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000501

AC:

AN:

1397316

Hom.:

Cov.:

AF XY:

0.00000870

AC XY:

AN XY:

689572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31582

American (AMR)

AF:

0.00

AC:

AN:

35778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25160

East Asian (EAS)

AF:

0.00

AC:

AN:

35742

South Asian (SAS)

AF:

0.00

AC:

AN:

79910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5562

European-Non Finnish (NFE)

AF:

0.00000649

AC:

AN:

1078456

Other (OTH)

AF:

0.00

AC:

AN:

57936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.23

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.091

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.32

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.34

MetaSVM

Uncertain

-0.099

MutationAssessor

Benign

1.2

PhyloP100

2.5

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.1

REVEL

Benign

0.21

Sift

Benign

0.19

Sift4G

Benign

0.070

Polyphen

0.42

Vest4

0.25

MutPred

0.36

Gain of sheet (P = 0.0344)

MVP

0.79

MPC

1.3

ClinPred

0.23

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.086

gMVP

0.78

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