12-66304734-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370285.1(HELB):​c.191C>A​(p.Ser64Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,425,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

HELB
NM_001370285.1 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.374
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07965782).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HELBNM_001370285.1 linkc.191C>A p.Ser64Tyr 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.191C>A p.Ser64Tyr missense_variant Exon 2 of 13 1 NM_001370285.1 ENSP00000247815.5 Q8NG08-1
HELBENST00000440906.6 linkn.191C>A non_coding_transcript_exon_variant Exon 2 of 12 1 ENSP00000396955.2 Q8NG08-2
HELBENST00000542394.5 linkn.191C>A non_coding_transcript_exon_variant Exon 2 of 13 1 ENSP00000439617.1 F5H1I4
HELBENST00000545134.1 linkn.191C>A non_coding_transcript_exon_variant Exon 2 of 14 2 ENSP00000443287.1 Q8NG08-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000210
AC:
3
AN:
1425348
Hom.:
0
Cov.:
33
AF XY:
0.00000283
AC XY:
2
AN XY:
706458
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:
0.00000182
Gnomad4 OTH exome
AF:
0.0000170
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.191C>A (p.S64Y) alteration is located in exon 2 (coding exon 2) of the HELB gene. This alteration results from a C to A substitution at nucleotide position 191, causing the serine (S) at amino acid position 64 to be replaced by a tyrosine (Y). 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
0.12
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
6.7
DANN
Benign
0.87
DEOGEN2
Benign
0.0059
T
Eigen
Benign
-0.95
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.041
N
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.080
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.44
N
REVEL
Benign
0.047
Sift
Benign
0.062
T
Sift4G
Benign
0.12
T
Polyphen
0.76
P
Vest4
0.18
MutPred
0.38
Gain of catalytic residue at L61 (P = 0);
MVP
0.19
MPC
0.25
ClinPred
0.16
T
GERP RS
-2.0
Varity_R
0.052
gMVP
0.17

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: chr12-66698514; API