rs768797926

Variant summary

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

The NM_004260.4(RECQL4):​c.2714C>T​(p.Pro905Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

2
5
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32
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]

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
RECQL4NM_004260.4 linkc.2714C>T p.Pro905Leu missense_variant Exon 15 of 21 ENST00000617875.6 NP_004251.4 O94761

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RECQL4ENST00000617875.6 linkc.2714C>T p.Pro905Leu missense_variant Exon 15 of 21 1 NM_004260.4 ENSP00000482313.2 O94761

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1441992
Hom.:
0
Cov.:
66
AF XY:
0.00000140
AC XY:
1
AN XY:
715634
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000238
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:
9.07e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
ExAC
AF:
0.00000835
AC:
1

ClinVar

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

Submissions by phenotype

Baller-Gerold syndrome Uncertain:1
Oct 14, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 905 of the RECQL4 protein (p.Pro905Leu). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 406989). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RECQL4 protein function with a negative predictive value of 80%. In 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Benign
22
DANN
Benign
0.85
DEOGEN2
Benign
0.10
T;T
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.036
D
MetaRNN
Uncertain
0.55
D;D
MutationAssessor
Pathogenic
2.9
.;M
PrimateAI
Benign
0.48
T
Sift4G
Uncertain
0.047
D;D
Polyphen
0.97
.;D
Vest4
0.46
MVP
0.76
GERP RS
4.3
Varity_R
0.17
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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: rs768797926; hg19: chr8-145738271; API