rs794726912
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_004260.4(RECQL4):c.82C>T(p.Gln28Ter) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q28Q) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RECQL4
NM_004260.4 stop_gained, splice_region
NM_004260.4 stop_gained, splice_region
Scores
2
2
Splicing: ADA: 0.00004690
2
Clinical Significance
Conservation
PhyloP100: 0.589
Genes affected
RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 188 pathogenic variants in the truncated region.
PP5
?
Variant 8-144517703-G-A is Pathogenic according to our data. Variant chr8-144517703-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 193272.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-144517703-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.82C>T | p.Gln28Ter | stop_gained, splice_region_variant | 1/21 | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.82C>T | p.Gln28Ter | stop_gained, splice_region_variant | 1/21 | 1 | NM_004260.4 | P1 | |
RECQL4 | ENST00000621189.4 | c.-1055C>T | 5_prime_UTR_variant | 1/20 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1235402Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 606352
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1235402
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
606352
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 03, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Benign
FATHMM_MKL
Benign
N
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at