rs8080100

Variant names:

• chr17-67215926-C-T
• rs8080100
• NM_014877.4:c.220G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014877.4(HELZ):​c.220G>A​(p.Val74Met) variant causes a missense change. The variant allele was found at a frequency of 0.161 in 1,531,222 control chromosomes in the GnomAD database, including 21,148 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.20 (3027 hom., cov: 32)
  • Exomes 𝑓: 0.16 (18121 hom.)
• Consequence: HELZ NM_014877.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.20

Genes affected

HELZ (HGNC:16878): (helicase with zinc finger) HELZ is a member of the superfamily I class of RNA helicases. RNA helicases alter the conformation of RNA by unwinding double-stranded regions, thereby altering the biologic activity of the RNA molecule and regulating access to other proteins (Wagner et al., 1999 [PubMed 10471385]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002059728).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HELZ	NM_014877.4	c.220G>A	p.Val74Met	missense_variant	Exon 5 of 33	ENST00000358691.10	NP_055692.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HELZ	ENST00000358691.10	c.220G>A	p.Val74Met	missense_variant	Exon 5 of 33	1	NM_014877.4	ENSP00000351524.5

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29767 AN: 151878 Hom.: 3028 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.175

GnomAD3 exomes AF: 0.174 AC: 40275 AN: 232096 Hom.: 3617 AF XY: 0.173 AC XY: 21730 AN XY: 125470

Gnomad AFR exome AF: 0.256

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.189

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.157 AC: 217153 AN: 1379236 Hom.: 18121 Cov.: 25 AF XY: 0.158 AC XY: 108623 AN XY: 688888

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.196 AC: 29776 AN: 151986 Hom.: 3027 Cov.: 32 AF XY: 0.199 AC XY: 14772 AN XY: 74262

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.174

Alfa AF: 0.170 Hom.: 5819

Bravo AF: 0.192

TwinsUK AF: 0.173 AC: 643

ALSPAC AF: 0.162 AC: 624

ESP6500AA AF: 0.236 AC: 851

ESP6500EA AF: 0.161 AC: 1313

ExAC AF: 0.163 AC: 19633

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Benign	0.94
DEOGEN2	Benign	0.063	T;T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.59	T;T;T
MetaRNN	Benign	0.0021	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.020	N;.;.
REVEL	Benign	0.21
Sift	Uncertain	0.017	D;.;.
Sift4G	Benign	0.13	T;T;.
Polyphen		0.98	D;.;.
Vest4		0.11
MPC		0.69
ClinPred		0.021	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs8080100; hg19: chr17-65212042;