chr3-149039066-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003071.4(HLTF):c.2779G>T(p.Val927Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000316 in 1,581,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
HLTF
NM_003071.4 missense
NM_003071.4 missense
Scores
8
6
5
Clinical Significance
Conservation
PhyloP100: 4.66
Genes affected
HLTF (HGNC:11099): (helicase like transcription factor) This gene encodes a member of the SWI/SNF family. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein contains a RING finger DNA binding motif. Two transcript variants encoding the same protein have been found for this gene. However, use of an alternative translation start site produces an isoform that is truncated at the N-terminus compared to the full-length protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.88
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HLTF | NM_003071.4 | c.2779G>T | p.Val927Leu | missense_variant | 23/25 | ENST00000310053.10 | NP_003062.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HLTF | ENST00000310053.10 | c.2779G>T | p.Val927Leu | missense_variant | 23/25 | 1 | NM_003071.4 | ENSP00000308944 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152084Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 7.00e-7 AC: 1AN: 1429576Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1AN XY: 710384
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74302
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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 | Nov 18, 2022 | The c.2779G>T (p.V927L) alteration is located in exon 23 (coding exon 23) of the HLTF gene. This alteration results from a G to T substitution at nucleotide position 2779, causing the valine (V) at amino acid position 927 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;T;T;T;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;.;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;M;M;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Pathogenic
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;.
Polyphen
1.0
.;D;D;D;.
Vest4
MutPred
0.74
.;Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);.;
MVP
MPC
0.72
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at