NM_004260.4:c.3616G>C

Variant names:

• chr8-144511442-C-G
• NM_004260.4:c.3616G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004260.4(RECQL4):​c.3616G>C​(p.Val1206Leu) 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 (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.410

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]

MFSD3 (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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06705806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.3616G>C	p.Val1206Leu	missense_variant	Exon 21 of 21	ENST00000617875.6	NP_004251.4
MFSD3	NM_138431.3	c.*278C>G		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.3616G>C	p.Val1206Leu	missense_variant	Exon 21 of 21	1	NM_004260.4	ENSP00000482313.2
MFSD3	ENST00000301327.5	c.*278C>G		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

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3616G>C (p.V1206L) alteration is located in exon 21 (coding exon 21) of the RECQL4 gene. This alteration results from a G to C substitution at nucleotide position 3616, causing the valine (V) at amino acid position 1206 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.10
DANN	Benign	0.65
DEOGEN2	Benign	0.0023	T;T;T
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.47	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.067	T;T;T
MutationAssessor	Benign	0.0	.;N;.
PrimateAI	Benign	0.26	T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0010	.;B;.
Vest4		0.12
MVP		0.33
GERP RS		-2.6
Varity_R		0.021
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145736825;