HELLS p.Glu189Val

Variant names:

• chr10-94574048-A-T
• NM_018063.5:c.566A>T
• HELLS p.Glu189Val

Your query was ambiguous. Multiple possible variants found:

• chr10-94574048-A-T
• chr10-94574048-AA-TT
• chr10-94574048-AA-TC
• chr10-94574048-AA-TG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018063.5(HELLS):​c.566A>T​(p.Glu189Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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: HELLS NM_018063.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.22
• Publications: 0 publications found

Genes affected

HELLS (HGNC:4861): (helicase, lymphoid specific) This gene encodes a lymphoid-specific helicase. Other helicases function in processes involving DNA strand separation, including replication, repair, recombination, and transcription. This protein is thought to be involved with cellular proliferation and may play a role in leukemogenesis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jan 2014]

HELLS Gene-Disease associations (from GenCC):

• immunodeficiency-centromeric instability-facial anomalies syndrome 4

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• immunodeficiency-centromeric instability-facial anomalies syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3897938).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018063.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELLS	NM_018063.5	MANE Select	c.566A>T	p.Glu189Val	missense	Exon 8 of 22	NP_060533.2
	HELLS	NM_001289067.2		c.566A>T	p.Glu189Val	missense	Exon 8 of 23	NP_001275996.1	A0A0B4J1V9
	HELLS	NM_001289068.2		c.518A>T	p.Glu173Val	missense	Exon 8 of 22	NP_001275997.1	Q9NRZ9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HELLS	ENST00000348459.10	TSL:1 MANE Select	c.566A>T	p.Glu189Val	missense	Exon 8 of 22	ENSP00000239027.7	Q9NRZ9-1
	HELLS	ENST00000394036.6	TSL:1	c.566A>T	p.Glu189Val	missense	Exon 8 of 23	ENSP00000377601.2	A0A0B4J1V9
	HELLS	ENST00000394045.6	TSL:1	c.566A>T	p.Glu189Val	missense	Exon 8 of 20	ENSP00000377609.1	Q9NRZ9-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.48	D
MutationAssessor	Benign	0.81	L
PhyloP100		9.2
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.26
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.092	T
Varity_R		0.24
gMVP		0.39
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-96333805;