12-66304872-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001370285.1(HELB):​c.329C>T​(p.Pro110Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,461,858 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: not found (cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

HELB
NM_001370285.1 missense

Scores

5
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.19
Variant links:
Genes affected
HELB (HGNC:17196): (DNA helicase B) This gene encodes a DNA-dependent ATPase which catalyzes the unwinding of DNA necessary for DNA replication, repair, recombination, and transcription. This gene is thought to function specifically during the S phase entry of the cell cycle. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.764

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HELBNM_001370285.1 linkc.329C>T p.Pro110Leu missense_variant Exon 2 of 13 ENST00000247815.9 NP_001357214.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HELBENST00000247815.9 linkc.329C>T p.Pro110Leu missense_variant Exon 2 of 13 1 NM_001370285.1 ENSP00000247815.5 Q8NG08-1
HELBENST00000440906.6 linkn.329C>T non_coding_transcript_exon_variant Exon 2 of 12 1 ENSP00000396955.2 Q8NG08-2
HELBENST00000542394.5 linkn.329C>T non_coding_transcript_exon_variant Exon 2 of 13 1 ENSP00000439617.1 F5H1I4
HELBENST00000545134.1 linkn.329C>T non_coding_transcript_exon_variant Exon 2 of 14 2 ENSP00000443287.1 Q8NG08-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251458
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461858
Hom.:
0
Cov.:
33
AF XY:
0.0000193
AC XY:
14
AN XY:
727226
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:
0.0000464
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 28, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.329C>T (p.P110L) alteration is located in exon 2 (coding exon 2) of the HELB gene. This alteration results from a C to T substitution at nucleotide position 329, causing the proline (P) at amino acid position 110 to be replaced by a leucine (L). 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
0.79
BayesDel_addAF
Uncertain
0.015
T
BayesDel_noAF
Uncertain
-0.010
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.97
D
M_CAP
Benign
0.076
D
MetaRNN
Pathogenic
0.76
D
MetaSVM
Benign
-0.55
T
MutationAssessor
Uncertain
2.9
M
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-5.0
D
REVEL
Uncertain
0.39
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.87
MutPred
0.48
Gain of helix (P = 0.005);
MVP
0.69
MPC
0.68
ClinPred
0.98
D
GERP RS
5.0
Varity_R
0.62
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs201128308; hg19: chr12-66698652; COSMIC: COSV56072393; API