Genetic Variant HSBP1L1:p.Pro9Ser (chr18-79964760-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001136180.2(HSBP1L1):c.25C>T(p.Pro9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000318 in 1,414,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

HSBP1L1
NM_001136180.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.110

Variant links:

Genes affected

HSBP1L1 (HGNC:37243): (heat shock factor binding protein 1 like 1) Predicted to enable transcription corepressor activity. Predicted to be involved in cellular heat acclimation. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

HSBP1L1 links:

Genome browser will be placed here

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=0.1484108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSBP1L1	NM_001136180.2 link	c.25C>T	p.Pro9Ser	missense_variant	Exon 1 of 4	ENST00000451882.3	NP_001129652.1	C9JCN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HSBP1L1	ENST00000451882.3 link	c.25C>T	p.Pro9Ser	missense_variant	Exon 1 of 4	1	NM_001136180.2	ENSP00000414236.1	C9JCN9
HSBP1L1	ENST00000589516.1 link	n.25C>T		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000467108.1	K7ENV5
HSBP1L1	ENST00000592352.1 link	n.179C>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151600

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000341

AC:

AN:

1262418

Hom.:

Cov.:

AF XY:

0.0000339

AC XY:

AN XY:

620248

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:

0.0000309

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000383

Gnomad4 OTH exome

AF:

0.0000386

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151600

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74072

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.25C>T (p.P9S) alteration is located in exon 1 (coding exon 1) of the HSBP1L1 gene. This alteration results from a C to T substitution at nucleotide position 25, causing the proline (P) at amino acid position 9 to be replaced by a serine (S). 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

0.080

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0075

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.58

M_CAP

Benign

0.053

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.97

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.29

REVEL

Benign

0.077

Sift

Benign

0.058

Sift4G

Benign

0.24

Polyphen

0.99

Vest4

0.12

MutPred

0.17

Gain of phosphorylation at P9 (P = 0.0102);

MVP

0.081

ClinPred

0.19

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.059

gMVP

0.057

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