17-75628354-C-T

Variant summary

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

The NM_004259.7(RECQL5):​c.2669G>A​(p.Ser890Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S890T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RECQL5
NM_004259.7 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12
Variant links:
Genes affected
RECQL5 (HGNC:9950): (RecQ like helicase 5) The protein encoded by this gene is a helicase that is important for genome stability. The encoded protein also prevents aberrant homologous recombination by displacing RAD51 from ssDNA. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

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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=0.12159911).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RECQL5NM_004259.7 linkc.2669G>A p.Ser890Asn missense_variant Exon 18 of 20 ENST00000317905.10 NP_004250.4 O94762-1A0A024R8M9Q8WYH5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RECQL5ENST00000317905.10 linkc.2669G>A p.Ser890Asn missense_variant Exon 18 of 20 1 NM_004259.7 ENSP00000317636.5 O94762-1
RECQL5ENST00000423245.6 linkc.2588G>A p.Ser863Asn missense_variant Exon 18 of 20 1 ENSP00000394820.2 O94762-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461724
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727192
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
9.9
DANN
Benign
0.72
DEOGEN2
Benign
0.14
.;T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.59
FATHMM_MKL
Benign
0.047
N
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.1
.;M
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.12
.;N
REVEL
Benign
0.12
Sift
Benign
0.074
.;T
Sift4G
Benign
0.37
T;T
Polyphen
0.94
.;P
Vest4
0.27
MutPred
0.17
.;Gain of relative solvent accessibility (P = 0.0289);
MVP
0.64
MPC
0.12
ClinPred
0.19
T
GERP RS
3.0
Varity_R
0.037
gMVP
0.17

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-73624434; API