Variant 21-43630452-A-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_007031.2(HSF2BP):c.444T>A(p.Asp148Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,456,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.000010 ( 0 hom. )

Consequence

HSF2BP
NM_007031.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0820

Variant links:

Genes affected

HSF2BP (HGNC:5226): (heat shock transcription factor 2 binding protein) HSF2 binding protein (HSF2BP) associates with HSF2. The interaction occurs between the trimerization domain of HSF2 and the amino terminal hydrophilic region of HSF2BP that comprises two leucine zipper motifs. HSF2BP may therefore be involved in modulating HSF2 activation. [provided by RefSeq, Jul 2008]

HSF2BP 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=0.11033288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSF2BP	NM_007031.2 linkuse as main transcript	c.444T>A	p.Asp148Glu	missense_variant, splice_region_variant	6/9	ENST00000291560.7	NP_008962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSF2BP	ENST00000291560.7 linkuse as main transcript	c.444T>A	p.Asp148Glu	missense_variant, splice_region_variant	6/9	1	NM_007031.2	ENSP00000291560	P1	O75031-1
HSF2BP	ENST00000443485.1 linkuse as main transcript	c.453T>A	p.Asp151Glu	missense_variant, splice_region_variant	6/7	5		ENSP00000409585

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000408

AC:

AN:

245170

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132608

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1456554

Hom.:

Cov.:

AF XY:

0.00000966

AC XY:

AN XY:

724536

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

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

Jul 15, 2021

The c.444T>A (p.D148E) alteration is located in exon 6 (coding exon 5) of the HSF2BP gene. This alteration results from a T to A substitution at nucleotide position 444, causing the aspartic acid (D) at amino acid position 148 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

0.83

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.12

Sift

Benign

0.57

T;T

Sift4G

Benign

0.23

T;.

Polyphen

0.0010

B;.

Vest4

0.094

MutPred

0.22

Loss of sheet (P = 0.0315);.;

MVP

0.50

MPC

0.059

ClinPred

0.10

GERP RS

-2.6

Varity_R

0.027

gMVP

0.13

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