17-67107488-A-G

Position:

• chr17-67107488-A-G

Variant summary

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

The NM_014877.4(HELZ):​c.4922T>C​(p.Ile1641Thr) 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. 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)
• Consequence: HELZ NM_014877.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45

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=0.15425897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HELZ	NM_014877.4	c.4922T>C	p.Ile1641Thr	missense_variant	31/33	ENST00000358691.10	NP_055692.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELZ	ENST00000358691.10	c.4922T>C	p.Ile1641Thr	missense_variant	31/33	1	NM_014877.4	ENSP00000351524.5
HELZ	ENST00000580168.5	c.4925T>C	p.Ile1642Thr	missense_variant	31/33	1		ENSP00000464512.1
HELZ	ENST00000579953.5	n.*1589T>C		non_coding_transcript_exon_variant	29/31	2		ENSP00000463727.1
HELZ	ENST00000579953.5	n.*1589T>C		3_prime_UTR_variant	29/31	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

Feb 06, 2023

The c.4922T>C (p.I1641T) alteration is located in exon 31 (coding exon 28) of the HELZ gene. This alteration results from a T to C substitution at nucleotide position 4922, causing the isoleucine (I) at amino acid position 1641 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.075	T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.063
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.70	N;.
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D;.
Sift4G	Benign	0.40	T;T
Polyphen		0.0050	B;.
Vest4		0.41
MutPred		0.33		Loss of sheet (P = 0.0126);.;
MVP		0.15
MPC		0.21
ClinPred		0.67	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.18

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: chr17-65103604;