Genetic Variant HABP4:p.Pro307Ser (chr9-96484553-C-T) – 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_014282.4(HABP4):c.919C>T(p.Pro307Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,158 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. P307T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

HABP4
NM_014282.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.37

Publications

0 publications found

Variant links:

Genes affected

HABP4 (HGNC:17062): (hyaluronan binding protein 4) Enables SUMO binding activity. Involved in PML body organization; negative regulation of DNA binding activity; and positive regulation of gene expression. Located in several cellular components, including Golgi apparatus; cytoplasmic stress granule; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

HABP4 links:

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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=0.32116896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HABP4	NM_014282.4 link	c.919C>T	p.Pro307Ser	missense_variant	Exon 6 of 8	ENST00000375249.5	NP_055097.2	Q5JVS0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HABP4	ENST00000375249.5 link	c.919C>T	p.Pro307Ser	missense_variant	Exon 6 of 8	1	NM_014282.4	ENSP00000364398.4	Q5JVS0-1
HABP4	ENST00000375251.7 link	c.604C>T	p.Pro202Ser	missense_variant	Exon 3 of 5	1		ENSP00000364400.3	Q5JVS0-2
HABP4	ENST00000466976.1 link	n.1529C>T		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.47

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

.;T

Eigen

Pathogenic

0.68

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.6

.;M

PhyloP100

3.4

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.23

Sift

Benign

0.12

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.74

P;D

Vest4

0.38

MutPred

0.42

.;Gain of phosphorylation at P307 (P = 0.0148);

MVP

0.75

MPC

0.62

ClinPred

0.96

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.58

Mutation Taster

=82/18

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over