rs931761657

Positions:

• chr8-144513384-C-G
• chr8-144513384-C-T

Variant summary

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

The NM_004260.4(RECQL4):​c.2297G>C​(p.Arg766Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,418 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: 2.80

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]

(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.2297G>C	p.Arg766Pro	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.2297G>C	p.Arg766Pro	missense_variant	14/21	1	NM_004260.4	ENSP00000482313	P1
RECQL4	ENST00000621189.4	c.1226G>C	p.Arg409Pro	missense_variant	13/20	1		ENSP00000483145
	ENST00000580385.1	n.272-222C>G		intron_variant, non_coding_transcript_variant		3
RECQL4	ENST00000534626.6	c.634+32G>C		intron_variant		5		ENSP00000477457

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455418 Hom.: 0 Cov.: 48 AF XY: 0.00000138 AC XY: 1 AN XY: 724386

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.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.12	T;D
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.67	D;D
MutationAssessor	Benign	0.86	.;L
PrimateAI	Uncertain	0.60	T
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	.;D
Vest4		0.61
MVP		0.79
GERP RS		4.8
Varity_R		0.84
gMVP		0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs931761657; hg19: chr8-145738767;