rs769977498

Variant names:

• chr8-144513256-C-A
• NM_004260.4:c.2425G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144513256-C-A
• chr8-144513256-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004260.4(RECQL4):​c.2425G>T​(p.Gly809Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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]

ENSG00000265393 (HGNC:):

ACMG classification

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, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.2425G>T	p.Gly809Trp	missense_variant	Exon 14 of 21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.2425G>T	p.Gly809Trp	missense_variant	Exon 14 of 21	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.1354G>T	p.Gly452Trp	missense_variant	Exon 13 of 20	1		ENSP00000483145.1
RECQL4	ENST00000534626.6	c.634-118G>T		intron_variant	Intron 5 of 7	5		ENSP00000477457.1
ENSG00000265393	ENST00000580385.1	n.272-350C>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1438674 Hom.: 0 Cov.: 47 AF XY: 0.00 AC XY: 0 AN XY: 714820

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: 0.00

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	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Benign	0.90
DEOGEN2	Uncertain	0.50	D;D
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Pathogenic	0.37	D
MetaRNN	Pathogenic	0.83	D;D
MutationAssessor	Pathogenic	5.1	.;H
PrimateAI	Uncertain	0.70	T
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.69
MVP		0.64
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.53
gMVP		0.75

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: chr8-145738639; COSMIC: COSV105011920; COSMIC: COSV105011920;