8-144511448-G-T

Variant names:

• chr8-144511448-G-T
• NM_004260.4:c.3610C>A

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.3610C>A​(p.Leu1204Met) 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. 10/14 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. L1204Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.650
• 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]

SLC33A2 (HGNC:25157): (major facilitator superfamily domain containing 3) Predicted to enable solute:proton symporter activity. Predicted to be involved in proton transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13742653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.3610C>A	p.Leu1204Met	missense_variant	Exon 21 of 21	ENST00000617875.6	NP_004251.4
SLC33A2	NM_138431.3	c.*284G>T		downstream_gene_variant		ENST00000301327.5	NP_612440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.3610C>A	p.Leu1204Met	missense_variant	Exon 21 of 21	1	NM_004260.4	ENSP00000482313.2
MFSD3	ENST00000301327.5	c.*284G>T		downstream_gene_variant		1	NM_138431.3	ENSP00000301327.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

May 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.L1204M variant (also known as c.3610C>A), located in coding exon 21 of the RECQL4 gene, results from a C to A substitution at nucleotide position 3610. The leucine at codon 1204 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.83
DEOGEN2	Benign	0.027	T;T;T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.41	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T;T;T
MutationAssessor	Uncertain	2.6	.;M;.
PhyloP100		0.65
PrimateAI	Benign	0.32	T
Sift4G	Benign	0.068	T;D;D
Polyphen		0.99	.;D;.
Vest4		0.31
MVP		0.32
GERP RS		2.9
Varity_R		0.048
gMVP		0.38
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr8-145736831;