GeneBe

1-220880232-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_021958.4(HLX):​c.375A>G​(p.Gln125Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 34)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HLX
NM_021958.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00100

Publications

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

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP7
Synonymous conserved (PhyloP=-0.001 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HLXNM_021958.4 linkc.375A>G p.Gln125Gln synonymous_variant Exon 1 of 4 ENST00000366903.8 NP_068777.1 Q14774
HLX-AS1NR_046901.1 linkn.-92T>C upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HLXENST00000366903.8 linkc.375A>G p.Gln125Gln synonymous_variant Exon 1 of 4 1 NM_021958.4 ENSP00000355870.5 Q14774
ENSG00000286231ENST00000651706.1 linkn.843-962A>G intron_variant Intron 6 of 8 ENSP00000499157.1 A0A494C1P3

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458460
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
725424
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33436
American (AMR)
AF:
0.00
AC:
0
AN:
44618
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26078
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39384
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85278
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53220
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5752
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1110532
Other (OTH)
AF:
0.00
AC:
0
AN:
60162
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
2.2
DANN
Benign
0.48
PhyloP100
-0.0010
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs62621984; hg19: chr1-221053574; API