chr8-144512733-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004260.4(RECQL4):​c.2794C>T​(p.His932Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,459,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H932Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

2
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37
Variant links:
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1349456).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RECQL4NM_004260.4 linkuse as main transcriptc.2794C>T p.His932Tyr missense_variant 16/21 ENST00000617875.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RECQL4ENST00000617875.6 linkuse as main transcriptc.2794C>T p.His932Tyr missense_variant 16/211 NM_004260.4 P1
ENST00000580385.1 linkuse as main transcriptn.167G>A non_coding_transcript_exon_variant 1/23

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1459902
Hom.:
0
Cov.:
67
AF XY:
0.00000413
AC XY:
3
AN XY:
726216
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:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Baller-Gerold syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeSep 23, 2022In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 459434). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 932 of the RECQL4 protein (p.His932Tyr). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
18
DANN
Benign
0.77
DEOGEN2
Benign
0.030
T;T;T
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Benign
0.65
T;T;T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.13
T;T;T
MutationAssessor
Benign
0.0
.;N;.
PrimateAI
Benign
0.20
T
Sift4G
Uncertain
0.015
D;D;D
Polyphen
0.0
.;B;.
Vest4
0.22
MVP
0.26
GERP RS
4.3
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.3
Varity_R
0.068
gMVP
0.32

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1554897279; hg19: chr8-145738116; API