17-67078355-G-A

Position:

• chr17-67078355-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014877.4(HELZ):​c.5726C>T​(p.Pro1909Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HELZ NM_014877.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58

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 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=0.086722404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HELZ	NM_014877.4	c.5726C>T	p.Pro1909Leu	missense_variant	33/33	ENST00000358691.10	NP_055692.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELZ	ENST00000358691.10	c.5726C>T	p.Pro1909Leu	missense_variant	33/33	1	NM_014877.4	ENSP00000351524.5
HELZ	ENST00000580168.5	c.5729C>T	p.Pro1910Leu	missense_variant	33/33	1		ENSP00000464512.1
HELZ	ENST00000579953.5	n.*2393C>T		non_coding_transcript_exon_variant	31/31	2		ENSP00000463727.1
HELZ	ENST00000579953.5	n.*2393C>T		3_prime_UTR_variant	31/31	2		ENSP00000463727.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.5726C>T (p.P1909L) alteration is located in exon 33 (coding exon 30) of the HELZ gene. This alteration results from a C to T substitution at nucleotide position 5726, causing the proline (P) at amino acid position 1909 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	Benign	0.067
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.085	T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.018
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.15
Sift	Benign	0.18	T;.
Sift4G	Benign	0.28	T;T
Polyphen		0.067	B;.
Vest4		0.19
MutPred		0.38		Loss of glycosylation at P1909 (P = 0.0013);.;
MVP		0.16
MPC		0.17
ClinPred		0.32	T
GERP RS		4.5
Varity_R		0.098
gMVP		0.14

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: chr17-65074471;