rs747207862

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003071.4(HLTF):​c.2777G>C​(p.Arg926Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,429,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R926Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

HLTF
NM_003071.4 missense

Scores

8
10
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42
Variant links:
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, 0.919

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HLTFNM_003071.4 linkc.2777G>C p.Arg926Pro missense_variant Exon 23 of 25 ENST00000310053.10 NP_003062.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HLTFENST00000310053.10 linkc.2777G>C p.Arg926Pro missense_variant Exon 23 of 25 1 NM_003071.4 ENSP00000308944.5 Q14527-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.00e-7
AC:
1
AN:
1429560
Hom.:
0
Cov.:
31
AF XY:
0.00000141
AC XY:
1
AN XY:
710294
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.10e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.27
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.60
.;D;D;D;D
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.95
D;.;.;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.92
D;D;D;D;D
MetaSVM
Uncertain
0.45
D
MutationAssessor
Pathogenic
3.5
.;M;M;M;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-4.0
D;D;D;D;D
REVEL
Pathogenic
0.66
Sift
Uncertain
0.010
D;D;D;D;D
Sift4G
Uncertain
0.024
D;D;D;D;.
Polyphen
1.0
.;D;D;D;.
Vest4
0.87
MutPred
0.83
.;Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);.;
MVP
0.90
MPC
0.88
ClinPred
0.99
D
GERP RS
6.0
Varity_R
0.75
gMVP
0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-148756855; API