rs149641041

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_031266.3(HNRNPAB):c.899A>G(p.Tyr300Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000106 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

HNRNPAB
NM_031266.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

Publications

0 publications found

Variant links:

Genes affected

HNRNPAB (HGNC:5034): (heterogeneous nuclear ribonucleoprotein A/B) This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are produced by RNA polymerase II and are components of the heterogeneous nuclear RNA (hnRNA) complexes. They 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, which binds to one of the components of the multiprotein editosome complex, has two repeats of quasi-RRM (RNA recognition motif) domains that bind to RNAs. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

HNRNPAB links:

PHYKPL (HGNC:28249): (5-phosphohydroxy-L-lysine phospho-lyase) This is a nuclear gene encoding a mitochondrial enzyme that catalyzes the conversion of 5-phosphonooxy-L-lysine to ammonia, inorganic phosphate, and 2-aminoadipate semialdehyde. Mutations in this gene may cause phosphohydroxylysinuria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

PHYKPL Gene-Disease associations (from GenCC):

phosphohydroxylysinuria
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

PHYKPL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21936157).

BS2

High AC in GnomAd4 at 41 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031266.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HNRNPAB	NM_031266.3	MANE Select	c.899A>G	p.Tyr300Cys	missense	Exon 7 of 8	NP_112556.2	Q99729-2
PHYKPL	NM_153373.4	MANE Select	c.*32-1328T>C		intron	N/A	NP_699204.1	Q8IUZ5-1
HNRNPAB	NM_001437957.1		c.899A>G	p.Tyr300Cys	missense	Exon 6 of 7	NP_001424886.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HNRNPAB	ENST00000358344.8	TSL:1 MANE Select	c.899A>G	p.Tyr300Cys	missense	Exon 7 of 8	ENSP00000351108.3	Q99729-2
HNRNPAB	ENST00000504898.5	TSL:1	c.899A>G	p.Tyr300Cys	missense	Exon 6 of 7	ENSP00000425031.1	Q99729-2
PHYKPL	ENST00000308158.10	TSL:1 MANE Select	c.*32-1328T>C		intron	N/A	ENSP00000310978.5	Q8IUZ5-1

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000147

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000875

AC:

AN:

251288

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.000924

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:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000889

AC:

130

AN:

1461568

Hom.:

Cov.:

AF XY:

0.0000894

AC XY:

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000792

AC:

AN:

1111746

Other (OTH)

AF:

0.000149

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.000269

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.000722

AC:

AN:

41574

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

67998

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000313

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

0.22

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.22

MetaSVM

Uncertain

0.69

MutationAssessor

Pathogenic

2.9

PhyloP100

4.9

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.62

Sift

Uncertain

0.0060

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.67

MVP

0.84

MPC

0.60

ClinPred

0.22

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.67

Mutation Taster

=39/61

disease causing

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over