rs767722327

chr8-144513102-C-Gchr8-144513102-C-T

Variant summary

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

The NM_004260.4(RECQL4):c.2500G>C(p.Ala834Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. A834T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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	UniProt
RECQL4	NM_004260.4	c.2500G>C	p.Ala834Pro	missense_variant	15/21	ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6	c.2500G>C	p.Ala834Pro	missense_variant	15/21	1	NM_004260.4	P1
RECQL4	ENST00000621189.4	c.1429G>C	p.Ala477Pro	missense_variant	14/20	1
	ENST00000580385.1	n.271+265C>G		intron_variant, non_coding_transcript_variant		3
RECQL4	ENST00000534626.6	c.673G>C	p.Ala225Pro	missense_variant	6/8	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
Cadd	Benign	20
Dann	Benign	0.55
DEOGEN2	Benign	0.084	T;T
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.72	D;D
PrimateAI	Benign	0.46	T
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	.;D
Vest4		0.62
MVP		0.69
GERP RS		4.2
Varity_R		0.073
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr8-145738485;