rs771381171

Variant names:

• chr8-144512404-C-G
• rs771381171
• NM_004260.4:c.3043G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-144512404-C-G
• chr8-144512404-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004260.4(RECQL4):​c.3043G>C​(p.Glu1015Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1015K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 35)
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0360
• Publications: 0 publications found

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]

RECQL4 Gene-Disease associations (from GenCC):

• Baller-Gerold syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• Rothmund-Thomson syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Rothmund-Thomson syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• osteosarcoma

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• rapadilino syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000265393 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11541706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.3043G>C	p.Glu1015Gln	missense	Exon 17 of 21	NP_004251.4	O94761
	RECQL4	NM_001413019.1		c.3118G>C	p.Glu1040Gln	missense	Exon 16 of 20	NP_001399948.1
	RECQL4	NM_001413036.1		c.3043G>C	p.Glu1015Gln	missense	Exon 17 of 21	NP_001399965.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.3043G>C	p.Glu1015Gln	missense	Exon 17 of 21	ENSP00000482313.2	O94761
	RECQL4	ENST00000621189.4	TSL:1	c.1972G>C	p.Glu658Gln	missense	Exon 16 of 20	ENSP00000483145.1	A0A087X072
	RECQL4	ENST00000971710.1		c.2950G>C	p.Glu984Gln	missense	Exon 17 of 21	ENSP00000641769.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 79

GnomAD4 genome Cov.: 35

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Baller-Gerold syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.6
DANN	Benign	0.48
DEOGEN2	Benign	0.021	T
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.12	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.036
PrimateAI	Benign	0.36	T
Sift4G	Benign	0.41	T
Polyphen		0.10	B
Vest4		0.15
MVP		0.75
GERP RS		-0.33
Varity_R		0.049
gMVP		0.34
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs771381171; hg19: chr8-145737787;