8-144517778-G-C

Variant names:

• chr8-144517778-G-C
• rs886042531
• NM_004260.4:c.7C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004260.4(RECQL4):​c.7C>G​(p.Arg3Gly) 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. 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. R3L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.879
• 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]

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32785124).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.7C>G	p.Arg3Gly	missense	Exon 1 of 21	NP_004251.4
	RECQL4	NM_001413019.1		c.7C>G	p.Arg3Gly	missense	Exon 1 of 20	NP_001399948.1
	RECQL4	NM_001413036.1		c.7C>G	p.Arg3Gly	missense	Exon 1 of 21	NP_001399965.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.7C>G	p.Arg3Gly	missense	Exon 1 of 21	ENSP00000482313.2
	RECQL4	ENST00000621189.4	TSL:1	c.-1130C>G		5_prime_UTR	Exon 1 of 20	ENSP00000483145.1
	LRRC14	ENST00000292524.6	TSL:1 MANE Select	c.-375G>C		upstream_gene	N/A	ENSP00000292524.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1087402 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 521108

African (AFR) AF: 0.00 AC: 0 AN: 21920

American (AMR) AF: 0.00 AC: 0 AN: 10936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15088

East Asian (EAS) AF: 0.00 AC: 0 AN: 23028

South Asian (SAS) AF: 0.00 AC: 0 AN: 30100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2926

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 919070

Other (OTH) AF: 0.00 AC: 0 AN: 42376

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Aug 30, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7C>G (p.R3G) alteration is located in exon 1 (coding exon 1) of the RECQL4 gene. This alteration results from a C to G substitution at nucleotide position 7, causing the arginine (R) at amino acid position 3 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Baller-Gerold syndrome Uncertain:1

Apr 07, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ClinVar contains an entry for this variant (Variation ID: 406919). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 3 of the RECQL4 protein (p.Arg3Gly). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Benign	0.90
DEOGEN2	Benign	0.30	T
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.33	T
PhyloP100		0.88
PrimateAI	Pathogenic	0.87	D
Sift4G	Uncertain	0.014	D
Polyphen		0.99	D
Vest4		0.24
MVP		0.63
GERP RS		3.4
PromoterAI		0.14	Neutral
Varity_R		0.39
gMVP		0.11
Mutation Taster		=78/22	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: rs886042531; hg19: chr8-145743162;