17-75628279-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004259.7(RECQL5):c.2744C>T(p.Ala915Val) variant causes a missense change. 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RECQL5 NM_004259.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26

Genes affected

RECQL5 (HGNC:9950): (RecQ like helicase 5) The protein encoded by this gene is a helicase that is important for genome stability. The encoded protein also prevents aberrant homologous recombination by displacing RAD51 from ssDNA. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23634434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL5	NM_004259.7	c.2744C>T	p.Ala915Val	missense_variant	18/20	ENST00000317905.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL5	ENST00000317905.10	c.2744C>T	p.Ala915Val	missense_variant	18/20	1	NM_004259.7	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.2744C>T (p.A915V) alteration is located in exon 18 (coding exon 17) of the RECQL5 gene. This alteration results from a C to T substitution at nucleotide position 2744, causing the alanine (A) at amino acid position 915 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.0084	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	24
Dann	Uncertain	0.98
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Uncertain	-0.030	T
MutationTaster	Benign	0.99	D;D
PrimateAI	Benign	0.36	T
REVEL	Benign	0.24
Sift4G	Benign	0.93	T;T
Polyphen		0.91	.;P
Vest4		0.34
MutPred		0.26		.;Gain of sheet (P = 0.0344);
MVP		0.78
MPC		0.25
ClinPred		0.83	D
GERP RS		5.4
Varity_R		0.096
gMVP		0.11

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: chr17-73624359;