rs762667669

Variant names:

• chr8-144514007-T-A
• NM_004260.4:c.1979A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-144514007-T-A
• chr8-144514007-T-C

Variant summary

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

The NM_004260.4(RECQL4):​c.1979A>T​(p.Glu660Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,417,768 control chromosomes in the GnomAD database, with no homozygous occurrence. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

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]

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 rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.1979A>T	p.Glu660Val	missense_variant	Exon 12 of 21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.1979A>T	p.Glu660Val	missense_variant	Exon 12 of 21	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.908A>T	p.Glu303Val	missense_variant	Exon 11 of 20	1		ENSP00000483145.1
RECQL4	ENST00000534626.6	c.347A>T	p.Glu116Val	missense_variant	Exon 3 of 8	5		ENSP00000477457.1
RECQL4	ENST00000532846.2	c.833A>T	p.Glu278Val	missense_variant	Exon 8 of 9	5		ENSP00000476551.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1417768 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 701590

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: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Baller-Gerold syndrome Uncertain:1

Sep 19, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 660 of the RECQL4 protein (p.Glu660Val). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RECQL4 protein function. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.00022	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Benign	0.59
DEOGEN2	Benign	0.065	T;T
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.55	D;D
PrimateAI	Benign	0.27	T
Sift4G	Benign	0.19	T;T
Polyphen		0.73	.;P
Vest4		0.49
MVP		0.69
GERP RS		1.6
Varity_R		0.24
gMVP		0.56

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: chr8-145739391;