NM_004260.4:c.3392G>C

Variant names:

• chr8-144511912-C-G
• NM_004260.4:c.3392G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004260.4(RECQL4):​c.3392G>C​(p.Arg1131Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1131K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RECQL4 NM_004260.4 missense, splice_region
• Scores: Splicing: ADA: 0.00002453
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09819645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.3392G>C	p.Arg1131Thr	missense_variant, splice_region_variant	Exon 19 of 21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.3392G>C	p.Arg1131Thr	missense_variant, splice_region_variant	Exon 19 of 21	1	NM_004260.4	ENSP00000482313.2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458254 Hom.: 0 Cov.: 57 AF XY: 0.00 AC XY: 0 AN XY: 725462

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	3.4
DANN	Benign	0.59
DEOGEN2	Benign	0.020	T;T;T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.098	T;T;T
MutationAssessor	Benign	1.1	.;L;.
PrimateAI	Benign	0.23	T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0020	.;B;.
Vest4		0.16
MVP		0.74
GERP RS		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.038
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.030		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: chr8-145737295;