8-144513978-C-G

Position:

• chr8-144513978-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004260.4(RECQL4):​c.2008G>C​(p.Val670Leu) 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. 10/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31857517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.2008G>C	p.Val670Leu	missense_variant	12/21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.2008G>C	p.Val670Leu	missense_variant	12/21	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.937G>C	p.Val313Leu	missense_variant	11/20	1		ENSP00000483145.1
RECQL4	ENST00000534626.6	c.376G>C	p.Val126Leu	missense_variant	3/8	5		ENSP00000477457.1
RECQL4	ENST00000532846.2	c.862G>C	p.Val288Leu	missense_variant	8/9	5		ENSP00000476551.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.1
DANN	Benign	0.61
DEOGEN2	Benign	0.0043	T;T
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.32	T;T
PrimateAI	Benign	0.30	T
Sift4G	Benign	0.67	T;T
Polyphen		0.0070	.;B
Vest4		0.44
MVP		0.69
GERP RS		1.7
Varity_R		0.049
gMVP		0.45

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145739362;