Genetic Variant NM_001136180.2:c.25C>T (chr18-79964760-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/20 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

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1484108).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136180.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSBP1L1	NM_001136180.2	MANE Select	c.25C>T	p.Pro9Ser	missense	Exon 1 of 4	NP_001129652.1	C9JCN9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSBP1L1	ENST00000451882.3	TSL:1 MANE Select	c.25C>T	p.Pro9Ser	missense	Exon 1 of 4	ENSP00000414236.1	C9JCN9
HSBP1L1	ENST00000903187.1		c.25C>T	p.Pro9Ser	missense	Exon 1 of 3	ENSP00000573246.1
HSBP1L1	ENST00000903186.1		c.25C>T	p.Pro9Ser	missense	Exon 1 of 2	ENSP00000573245.1

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

GnomAD2 exomes

AF:

0.00

AC:

AN:

46486

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000341

AC:

AN:

1262418

Hom.:

Cov.:

AF XY:

0.0000339

AC XY:

AN XY:

620248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25318

American (AMR)

AF:

0.00

AC:

AN:

19054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20384

East Asian (EAS)

AF:

0.00

AC:

AN:

27666

South Asian (SAS)

AF:

0.0000309

AC:

AN:

64730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4416

European-Non Finnish (NFE)

AF:

0.0000383

AC:

AN:

1017956

Other (OTH)

AF:

0.0000386

AC:

AN:

51778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

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:

0.0000132

AC:

AN:

151600

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74072

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41268

American (AMR)

AF:

0.00

AC:

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5090

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67840

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000142

Hom.:

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

0.080

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

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

PhyloP100

-0.11

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

PromoterAI

0.073

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.059

gMVP

0.057

Mutation Taster

=86/14

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

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