rs398124117
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PP3_Moderate
The NM_004260.4(RECQL4):c.2464-1G>T variant causes a splice acceptor change. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RECQL4
NM_004260.4 splice_acceptor
NM_004260.4 splice_acceptor
Scores
2
2
Splicing: ADA: 0.01681
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.88
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
?
Splicing variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 3.6, offset of -11, new splice context is: ccaccccaccctcatgaaAGttg. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PP3
?
BayesDel_addAF computational evidence supports a deleterious effect, 0.223
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RECQL4 | NM_004260.4 | c.2464-1G>T | splice_acceptor_variant | ENST00000617875.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RECQL4 | ENST00000617875.6 | c.2464-1G>T | splice_acceptor_variant | 1 | NM_004260.4 | P1 | |||
RECQL4 | ENST00000621189.4 | c.1393-1G>T | splice_acceptor_variant | 1 | |||||
ENST00000580385.1 | n.271+302C>A | intron_variant, non_coding_transcript_variant | 3 | ||||||
RECQL4 | ENST00000534626.6 | c.635-1G>T | splice_acceptor_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1409346Hom.: 0 Cov.: 66 AF XY: 0.00 AC XY: 0AN XY: 694262
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1409346
Hom.:
Cov.:
66
AF XY:
AC XY:
0
AN XY:
694262
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
?
Cov.:
34
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Uncertain
FATHMM_MKL
Pathogenic
D
GERP RS
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_AL_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.