NM_004260.4:c.1159G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004260.4(RECQL4):c.1159G>A(p.Gly387Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000364 in 1,612,860 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G387V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:6

Conservation

PhyloP100: -0.317

Publications

5 publications found

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]

RECQL4 Gene-Disease associations (from GenCC):

Baller-Gerold syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
Rothmund-Thomson syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Rothmund-Thomson syndrome type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P
osteosarcoma
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
rapadilino syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
congenital heart disease
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

RECQL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.054992676).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RECQL4	NM_004260.4	MANE Select	c.1159G>A	p.Gly387Arg	missense	Exon 6 of 21	NP_004251.4	O94761
RECQL4	NM_001413019.1		c.1159G>A	p.Gly387Arg	missense	Exon 6 of 20	NP_001399948.1
RECQL4	NM_001413036.1		c.1159G>A	p.Gly387Arg	missense	Exon 6 of 21	NP_001399965.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.1159G>A	p.Gly387Arg	missense	Exon 6 of 21	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4	TSL:1	c.88G>A	p.Gly30Arg	missense	Exon 5 of 20	ENSP00000483145.1	A0A087X072
RECQL4	ENST00000887977.1		c.1159G>A	p.Gly387Arg	missense	Exon 6 of 21	ENSP00000558036.1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000206

AC:

AN:

247044

AF XY:

0.000193

show subpopulations

Gnomad AFR exome

AF:

0.0000656

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000378

AC:

552

AN:

1460622

Hom.:

Cov.:

AF XY:

0.000365

AC XY:

265

AN XY:

726564

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000466

AC:

518

AN:

1111774

Other (OTH)

AF:

0.000530

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

108

144

180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000230

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000353

Hom.:

Bravo

AF:

0.000261

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000240

AC:

ExAC

AF:

0.000240

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000297

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Rothmund-Thomson syndrome type 2 (2)

Baller-Gerold syndrome (1)

Rothmund-Thomson syndrome;C0265308:Baller-Gerold syndrome;C1849453:Rapadilino syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.33

CADD

Benign

1.0

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.063

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.63

M_CAP

Benign

0.0043

MetaRNN

Benign

0.055

PhyloP100

-0.32

PrimateAI

Benign

0.24

Sift4G

Uncertain

0.032

Polyphen

0.035

Vest4

0.19

MVP

0.70

GERP RS

0.54

PromoterAI

-0.0072

Neutral

(source)

Varity_R

0.044

gMVP

0.36

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over