rs35842750

Variant names:

• chr8-144514991-C-G
• rs35842750
• NM_004260.4:c.1565G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-144514991-C-G
• chr8-144514991-C-T

Variant summary

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

The NM_004260.4(RECQL4):​c.1565G>C​(p.Arg522Pro) 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. R522C) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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.1565G>C	p.Arg522Pro	missense_variant	Exon 9 of 21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.1565G>C	p.Arg522Pro	missense_variant	Exon 9 of 21	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.494G>C	p.Arg165Pro	missense_variant	Exon 8 of 20	1		ENSP00000483145.1
RECQL4	ENST00000532846.2	c.419G>C	p.Arg140Pro	missense_variant	Exon 5 of 9	5		ENSP00000476551.1
RECQL4	ENST00000688394.1	n.588G>C		non_coding_transcript_exon_variant	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	21
DANN	Benign	0.80
DEOGEN2	Benign	0.073	T;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.71	D;D
PrimateAI	Benign	0.40	T
Sift4G	Uncertain	0.045	D;T
Polyphen		0.46	.;P
Vest4		0.60
MVP		0.78
GERP RS		5.5
Varity_R		0.67
gMVP		0.82

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

LitVar

Other links and lift over

dbSNP: rs35842750; hg19: chr8-145740375;