rs1368178192

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004260.4(RECQL4):​c.2328G>T​(p.Met776Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,453,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M776T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

8
2
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.82
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RECQL4NM_004260.4 linkuse as main transcriptc.2328G>T p.Met776Ile missense_variant 14/21 ENST00000617875.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RECQL4ENST00000617875.6 linkuse as main transcriptc.2328G>T p.Met776Ile missense_variant 14/211 NM_004260.4 P1
RECQL4ENST00000621189.4 linkuse as main transcriptc.1257G>T p.Met419Ile missense_variant 13/201
ENST00000580385.1 linkuse as main transcriptn.272-253C>A intron_variant, non_coding_transcript_variant 3
RECQL4ENST00000534626.6 linkuse as main transcriptc.634+63G>T intron_variant 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1453512
Hom.:
0
Cov.:
47
AF XY:
0.00000138
AC XY:
1
AN XY:
723460
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:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Pathogenic
0.32
CADD
Pathogenic
26
DANN
Benign
0.86
DEOGEN2
Benign
0.27
T;D
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Uncertain
0.23
D
MetaRNN
Pathogenic
0.77
D;D
MutationAssessor
Pathogenic
3.9
.;H
PrimateAI
Uncertain
0.74
T
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.76
MVP
0.35
GERP RS
5.7
Varity_R
0.95
gMVP
0.55

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: chr8-145738736; API