Genetic Variant HELB:p.Asn207Lys (chr12-66306358-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001370285.1(HELB):c.621T>G(p.Asn207Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000014 ( 0 hom. )

Consequence

HELB
NM_001370285.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.486

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]

HELB links:

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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=0.07232112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELB	NM_001370285.1 link	c.621T>G	p.Asn207Lys	missense_variant	Exon 3 of 13	ENST00000247815.9	NP_001357214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HELB	ENST00000247815.9 link	c.621T>G	p.Asn207Lys	missense_variant	Exon 3 of 13	1	NM_001370285.1	ENSP00000247815.5	Q8NG08-1
HELB	ENST00000440906.6 link	n.621T>G		non_coding_transcript_exon_variant	Exon 3 of 12	1		ENSP00000396955.2	Q8NG08-2
HELB	ENST00000542394.5 link	n.621T>G		non_coding_transcript_exon_variant	Exon 3 of 13	1		ENSP00000439617.1	F5H1I4
HELB	ENST00000545134.1 link	n.621T>G		non_coding_transcript_exon_variant	Exon 3 of 14	2		ENSP00000443287.1	Q8NG08-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000430

AC:

AN:

232716

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126172

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1438450

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715298

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000252

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:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.621T>G (p.N207K) alteration is located in exon 3 (coding exon 3) of the HELB gene. This alteration results from a T to G substitution at nucleotide position 621, causing the asparagine (N) at amino acid position 207 to be replaced by a lysine (K). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0035

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.095

M_CAP

Benign

0.011

MetaRNN

Benign

0.072

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.93

REVEL

Benign

0.032

Sift

Benign

0.33

Sift4G

Benign

0.32

Polyphen

0.17

Vest4

0.16

MutPred

0.44

Gain of methylation at N207 (P = 0.0122);

MVP

0.072

MPC

0.21

ClinPred

0.044

GERP RS

3.5

Varity_R

0.085

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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