rs747445357

Positions:

• chr8-144513417-C-A
• chr8-144513417-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004260.4(RECQL4):​c.2264G>T​(p.Arg755Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,840 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.2264G>T	p.Arg755Leu	missense_variant	14/21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.2264G>T	p.Arg755Leu	missense_variant	14/21	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.1193G>T	p.Arg398Leu	missense_variant	13/20	1		ENSP00000483145.1
RECQL4	ENST00000534626.6	c.632G>T	p.Arg211Leu	missense_variant, splice_region_variant	5/8	5		ENSP00000477457.1
ENSG00000265393	ENST00000580385.1	n.272-189C>A		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000830 AC: 2 AN: 241012 Hom.: 0 AF XY: 0.00000755 AC XY: 1 AN XY: 132464

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000560

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000917

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456840 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 724958

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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

Bravo AF: 0.00000378

ExAC AF: 0.00000834 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Pathogenic	0.21
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.074	T;T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.71	D;D
PrimateAI	Uncertain	0.56	T
Sift4G	Benign	0.17	T;D
Polyphen		0.90	.;P
Vest4		0.64
MVP		0.69
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.76
gMVP		0.66

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

LitVar

Other links and lift over

dbSNP: rs747445357; hg19: chr8-145738801;