chr17-55265509-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002126.5(HLF):​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 0.0000131 in 1,608,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

HLF
NM_002126.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09
Variant links:
Genes affected
HLF (HGNC:4977): (HLF transcription factor, PAR bZIP family member) This gene encodes a member of the proline and acidic-rich (PAR) protein family, a subset of the bZIP transcription factors. The encoded protein forms homodimers or heterodimers with other PAR family members and binds sequence-specific promoter elements to activate transcription. Chromosomal translocations fusing portions of this gene with the E2A gene cause a subset of childhood B-lineage acute lymphoid leukemias. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09425643).
BS2
High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HLFNM_002126.5 linkc.25C>T p.Pro9Ser missense_variant Exon 1 of 4 ENST00000226067.10 NP_002117.1 Q16534-1
HLFXM_005257269.3 linkc.25C>T p.Pro9Ser missense_variant Exon 1 of 4 XP_005257326.1
HLFXR_002957996.2 linkn.550C>T non_coding_transcript_exon_variant Exon 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HLFENST00000226067.10 linkc.25C>T p.Pro9Ser missense_variant Exon 1 of 4 1 NM_002126.5 ENSP00000226067.5 Q16534-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152070
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000818
AC:
2
AN:
244354
Hom.:
0
AF XY:
0.00000755
AC XY:
1
AN XY:
132504
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000592
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:
0.0000137
AC:
20
AN:
1456116
Hom.:
0
Cov.:
30
AF XY:
0.0000179
AC XY:
13
AN XY:
724502
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000450
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:
0.0000153
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152070
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000302

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 01, 2025
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 HLF 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
0.068
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.47
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.053
T
Eigen
Benign
0.037
Eigen_PC
Benign
0.068
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.094
T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
1.9
M
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-0.26
N
REVEL
Benign
0.061
Sift
Uncertain
0.025
D
Sift4G
Uncertain
0.026
D
Polyphen
0.58
P
Vest4
0.15
MutPred
0.15
Gain of phosphorylation at P9 (P = 0.0542);
MVP
0.082
MPC
0.95
ClinPred
0.61
D
GERP RS
3.1
Varity_R
0.082
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs759022481; hg19: chr17-53342870; API