rs1060499747

Positions:

• chr17-67128716-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PP5_Moderate BP4

The NM_014877.4(HELZ):​c.3322A>G​(p.Ile1108Val) 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 Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HELZ NM_014877.4 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.73

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]

HELZ (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-67128716-T-C is Pathogenic according to our data. Variant chr17-67128716-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 402158.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-67128716-T-C is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.2188293). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HELZ	NM_014877.4	c.3322A>G	p.Ile1108Val	missense_variant	24/33	ENST00000358691.10	NP_055692.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HELZ	ENST00000358691.10	c.3322A>G	p.Ile1108Val	missense_variant	24/33	1	NM_014877.4	ENSP00000351524.5
HELZ	ENST00000580168.5	c.3325A>G	p.Ile1109Val	missense_variant	24/33	1		ENSP00000464512.1
HELZ	ENST00000579953.5	n.3325A>G		non_coding_transcript_exon_variant	22/31	2		ENSP00000463727.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Abnormal brain morphology Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.063	T;T
Eigen	Benign	-0.065
Eigen_PC	Benign	0.087
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.97	L;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	0.010	N;.
REVEL	Benign	0.27
Sift	Benign	0.18	T;.
Sift4G	Benign	0.72	T;T
Polyphen		0.084	B;.
Vest4		0.31
MutPred		0.38		Gain of disorder (P = 0.1565);.;
MVP		0.19
MPC		0.60
ClinPred		0.58	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.077
gMVP		0.49

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: rs1060499747; hg19: chr17-65124832;