8-144514026-G-C

Variant summary

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

The NM_004260.4(RECQL4):​c.1960C>G​(p.Gln654Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,421,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38
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=0.22615719).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RECQL4NM_004260.4 linkc.1960C>G p.Gln654Glu missense_variant Exon 12 of 21 ENST00000617875.6 NP_004251.4 O94761

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RECQL4ENST00000617875.6 linkc.1960C>G p.Gln654Glu missense_variant Exon 12 of 21 1 NM_004260.4 ENSP00000482313.2 O94761
RECQL4ENST00000621189.4 linkc.889C>G p.Gln297Glu missense_variant Exon 11 of 20 1 ENSP00000483145.1 A0A087X072
RECQL4ENST00000534626.6 linkc.328C>G p.Gln110Glu missense_variant Exon 3 of 8 5 ENSP00000477457.1 V9GZ64
RECQL4ENST00000532846.2 linkc.814C>G p.Gln272Glu missense_variant Exon 8 of 9 5 ENSP00000476551.1 V9GYA3

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
7.03e-7
AC:
1
AN:
1421938
Hom.:
0
Cov.:
36
AF XY:
0.00000142
AC XY:
1
AN XY:
704042
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:
9.15e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.077
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
13
DANN
Benign
0.69
DEOGEN2
Benign
0.0074
T;T
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.23
T;T
PrimateAI
Benign
0.21
T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
.;B
Vest4
0.35
MVP
0.75
GERP RS
0.22
Varity_R
0.20
gMVP
0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145739410; API