rs368236790

Variant summary

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

The NM_005335.6(HCLS1):​c.1204G>T​(p.Glu402*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HCLS1
NM_005335.6 stop_gained

Scores

4
2
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.24
Variant links:
Genes affected
HCLS1 (HGNC:4844): (hematopoietic cell-specific Lyn substrate 1) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and protein kinase binding activity. Involved in several processes, including positive regulation of intracellular signal transduction; positive regulation of protein phosphorylation; and regulation of transcription, DNA-templated. Located in cytosol; nucleus; and plasma membrane. Part of transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HCLS1NM_005335.6 linkc.1204G>T p.Glu402* stop_gained Exon 12 of 14 ENST00000314583.8 NP_005326.3 P14317-1
HCLS1NM_001292041.2 linkc.1093G>T p.Glu365* stop_gained Exon 11 of 13 NP_001278970.2 P14317

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HCLS1ENST00000314583.8 linkc.1204G>T p.Glu402* stop_gained Exon 12 of 14 1 NM_005335.6 ENSP00000320176.3 P14317-1
HCLS1ENST00000428394.6 linkc.1093G>T p.Glu365* stop_gained Exon 11 of 13 2 ENSP00000387645.2 E7EVW7
HCLS1ENST00000473883.5 linkn.2007G>T non_coding_transcript_exon_variant Exon 7 of 9 2
HCLS1ENST00000495491.5 linkn.*519G>T downstream_gene_variant 2 ENSP00000418299.1 P14317-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461882
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.61
D
BayesDel_noAF
Pathogenic
0.63
CADD
Pathogenic
38
DANN
Uncertain
1.0
Eigen
Pathogenic
0.74
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.98
D
Vest4
0.64
GERP RS
5.2

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: chr3-121351215; API