8-144515989-T-G

Variant names:

• chr8-144515989-T-G
• NM_004260.4:c.1130A>C

Variant summary

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

The NM_004260.4(RECQL4):​c.1130A>C​(p.Gln377Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,328 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RECQL4 NM_004260.4 missense, splice_region
• Scores: Splicing: ADA: 0.006918
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4	c.1130A>C	p.Gln377Pro	missense_variant, splice_region_variant	Exon 5 of 21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6	c.1130A>C	p.Gln377Pro	missense_variant, splice_region_variant	Exon 5 of 21	1	NM_004260.4	ENSP00000482313.2
RECQL4	ENST00000621189.4	c.59A>C	p.Gln20Pro	missense_variant, splice_region_variant	Exon 4 of 20	1		ENSP00000483145.1
RECQL4	ENST00000532846.2	c.14A>C	p.Gln5Pro	missense_variant, splice_region_variant	Exon 1 of 9	5		ENSP00000476551.1
RECQL4	ENST00000524998.1	c.650A>C	p.Gln217Pro	missense_variant, splice_region_variant	Exon 3 of 4	3		ENSP00000476579.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457328 Hom.: 0 Cov.: 65 AF XY: 0.00 AC XY: 0 AN XY: 724250

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Benign	0.87
DEOGEN2	Benign	0.071	T;T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0070	T
MetaRNN	Uncertain	0.70	D;D
PrimateAI	Benign	0.40	T
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	.;D
Vest4		0.68
MVP		0.75
GERP RS		4.4
Varity_R		0.32
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0069
dbscSNV1_RF	Benign	0.064
SpliceAI score (max)		0.030		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: chr8-145741373;