rs780474951

Variant names:

• chr8-144513071-C-G
• NM_004260.4:c.2531G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-144513071-C-G
• chr8-144513071-C-T

Variant summary

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

The NM_004260.4(RECQL4):​c.2531G>C​(p.Arg844Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.801

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2603744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.2531G>C	p.Arg844Thr	missense_variant	Exon 15 of 21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.2531G>C	p.Arg844Thr	missense_variant	Exon 15 of 21	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.1460G>C	p.Arg487Thr	missense_variant	Exon 14 of 20	1		ENSP00000483145.1
RECQL4	ENST00000534626.6	c.701G>C	p.Arg234Thr	missense_variant	Exon 6 of 8	5		ENSP00000477457.1
ENSG00000265393	ENST00000580385.1	n.271+234C>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426366 Hom.: 0 Cov.: 66 AF XY: 0.00 AC XY: 0 AN XY: 705452

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: 9.15e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.1
DANN	Benign	0.72
DEOGEN2	Benign	0.086	T;T
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.26	T;T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Benign	0.41	T
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.57	.;P
Vest4		0.33
MVP		0.74
GERP RS		-4.0
Varity_R		0.13
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr8-145738454;