Variant 9-96465339-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014282.4(HABP4):c.515C>T(p.Pro172Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,450,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HABP4
NM_014282.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13979244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HABP4	NM_014282.4 linkuse as main transcript	c.515C>T	p.Pro172Leu	missense_variant, splice_region_variant	3/8	ENST00000375249.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HABP4	ENST00000375249.5 linkuse as main transcript	c.515C>T	p.Pro172Leu	missense_variant, splice_region_variant	3/8	1	NM_014282.4	P1	Q5JVS0-1
HABP4	ENST00000375251.7 linkuse as main transcript	c.512+6798C>T		intron_variant		1			Q5JVS0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250918

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000207

AC:

AN:

1450366

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2023

The c.515C>T (p.P172L) alteration is located in exon 3 (coding exon 3) of the HABP4 gene. This alteration results from a C to T substitution at nucleotide position 515, causing the proline (P) at amino acid position 172 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.74

M_CAP

Benign

0.037

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.067

Sift

Uncertain

0.029

Sift4G

Uncertain

0.0030

Polyphen

0.015

Vest4

0.34

MutPred

0.22

Gain of MoRF binding (P = 0.0618);

MVP

0.50

MPC

0.29

ClinPred

0.81

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over