3-121634325-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005335.6(HCLS1):c.785C>T(p.Ala262Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
HCLS1
NM_005335.6 missense
NM_005335.6 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 4.25
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]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCLS1 | NM_005335.6 | c.785C>T | p.Ala262Val | missense_variant | 10/14 | ENST00000314583.8 | |
HCLS1 | NM_001292041.2 | c.674C>T | p.Ala225Val | missense_variant | 9/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCLS1 | ENST00000314583.8 | c.785C>T | p.Ala262Val | missense_variant | 10/14 | 1 | NM_005335.6 | P1 | |
HCLS1 | ENST00000428394.6 | c.674C>T | p.Ala225Val | missense_variant | 9/13 | 2 | |||
HCLS1 | ENST00000473883.5 | n.1588C>T | non_coding_transcript_exon_variant | 5/9 | 2 | ||||
HCLS1 | ENST00000495491.5 | c.*100C>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251224Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135772
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461818Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 727224
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 26, 2022 | The c.785C>T (p.A262V) alteration is located in exon 10 (coding exon 9) of the HCLS1 gene. This alteration results from a C to T substitution at nucleotide position 785, causing the alanine (A) at amino acid position 262 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at