17-75628354-C-T

Variant names:

• chr17-75628354-C-T
• NM_004259.7:c.2669G>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.2669G>A​(p.Ser890Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S890T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RECQL5 NM_004259.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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=0.12159911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL5	NM_004259.7	c.2669G>A	p.Ser890Asn	missense_variant	Exon 18 of 20	ENST00000317905.10	NP_004250.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL5	ENST00000317905.10	c.2669G>A	p.Ser890Asn	missense_variant	Exon 18 of 20	1	NM_004259.7	ENSP00000317636.5
RECQL5	ENST00000423245.6	c.2588G>A	p.Ser863Asn	missense_variant	Exon 18 of 20	1		ENSP00000394820.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461724 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.9
DANN	Benign	0.72
DEOGEN2	Benign	0.14	.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.12	.;N
REVEL	Benign	0.12
Sift	Benign	0.074	.;T
Sift4G	Benign	0.37	T;T
Polyphen		0.94	.;P
Vest4		0.27
MutPred		0.17		.;Gain of relative solvent accessibility (P = 0.0289);
MVP		0.64
MPC		0.12
ClinPred		0.19	T
GERP RS		3.0
Varity_R		0.037
gMVP		0.17

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: chr17-73624434;