dbSNP rs375880001: HLX:p.Ile230Leu (chr1-220881289-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021958.4(HLX):c.688A>C(p.Ile230Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I230V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

HLX
NM_021958.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.90

Publications

0 publications found

Variant links:

Genes affected

HLX (HGNC:4978): (H2.0 like homeobox) Enables sequence-specific DNA binding activity. Predicted to be involved in cell differentiation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including animal organ development; enteric nervous system development; and regulation of T-helper cell differentiation. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

HLX links:

ENSG00000286231 (HGNC:):

ENSG00000286231 links:

HLX-AS1 (HGNC:42509): (HLX antisense RNA 1)

HLX-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22032797).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021958.4. 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
	HLX	NM_021958.4	MANE Select	c.688A>C	p.Ile230Leu	missense	Exon 2 of 4	NP_068777.1	Q14774

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HLX	ENST00000366903.8	TSL:1 MANE Select	c.688A>C	p.Ile230Leu	missense	Exon 2 of 4	ENSP00000355870.5	Q14774
ENSG00000286231	ENST00000651706.1		n.938A>C		non_coding_transcript_exon	Exon 7 of 9	ENSP00000499157.1	A0A494C1P3
HLX	ENST00000944514.1		c.688A>C	p.Ile230Leu	missense	Exon 2 of 4	ENSP00000614573.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111930

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.070

Eigen

Benign

-0.19

Eigen_PC

Benign

0.067

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.60

M_CAP

Benign

0.024

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.46

PhyloP100

6.9

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.48

REVEL

Benign

0.21

Sift

Benign

0.18

Sift4G

Benign

0.65

Polyphen

0.0010

Vest4

0.37

MutPred

0.20

Gain of disorder (P = 0.0532)

MVP

0.72

MPC

0.46

ClinPred

0.69

GERP RS

5.8

PromoterAI

0.013

Neutral

(source)

Varity_R

0.20

gMVP

0.16

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over