Variant 17-55315408-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_002126.5(HLF):c.633C>G(p.Ile211Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I211F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

HLF
NM_002126.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.772

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]

HLF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3049739).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HLF	NM_002126.5 linkuse as main transcript	c.633C>G	p.Ile211Met	missense_variant	3/4	ENST00000226067.10
HLF	NM_001330375.2 linkuse as main transcript	c.378C>G	p.Ile126Met	missense_variant	3/4
HLF	XM_005257269.3 linkuse as main transcript	c.633C>G	p.Ile211Met	missense_variant	3/4
HLF	XM_047435895.1 linkuse as main transcript	c.378C>G	p.Ile126Met	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLF	ENST00000226067.10 linkuse as main transcript	c.633C>G	p.Ile211Met	missense_variant	3/4	1	NM_002126.5	P1	Q16534-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251246

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135774

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727238

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

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

Mar 14, 2023

The c.633C>G (p.I211M) alteration is located in exon 3 (coding exon 3) of the HLF gene. This alteration results from a C to G substitution at nucleotide position 633, causing the isoleucine (I) at amino acid position 211 to be replaced by a methionine (M). 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

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Benign

-0.13

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.17

T;.;.;.;T

Eigen

Benign

-0.053

Eigen_PC

Benign

-0.045

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.84

T;.;.;T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.30

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

L;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.1

N;N;.;.;.

REVEL

Benign

0.21

Sift

Benign

0.17

T;T;.;.;.

Sift4G

Benign

0.12

T;T;T;T;T

Polyphen

1.0

D;.;.;.;.

Vest4

0.60

MutPred

0.29

Loss of methylation at K212 (P = 0.0191);.;.;.;.;

MVP

0.43

MPC

1.8

ClinPred

0.84

GERP RS

1.7

Varity_R

0.15

gMVP

0.76

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