chr8-144517731-G-T

Variant names:

• chr8-144517731-G-T
• NM_004260.4:c.54C>A
• RECQL4 p.Phe18Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004260.4(RECQL4):​c.54C>A​(p.Phe18Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F18S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RECQL4 NM_004260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.626
• Publications: 0 publications found

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]

LRRC14 (HGNC:20419): (leucine rich repeat containing 14) This gene encodes a leucine-rich repeat-containing protein. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3973376).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	NM_004260.4	MANE Select	c.54C>A	p.Phe18Leu	missense	Exon 1 of 21	NP_004251.4	O94761
	RECQL4	NM_001413019.1		c.54C>A	p.Phe18Leu	missense	Exon 1 of 20	NP_001399948.1
	RECQL4	NM_001413036.1		c.54C>A	p.Phe18Leu	missense	Exon 1 of 21	NP_001399965.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RECQL4	ENST00000617875.6	TSL:1 MANE Select	c.54C>A	p.Phe18Leu	missense	Exon 1 of 21	ENSP00000482313.2	O94761
	RECQL4	ENST00000621189.4	TSL:1	c.-1083C>A		5_prime_UTR	Exon 1 of 20	ENSP00000483145.1	A0A087X072
	RECQL4	ENST00000971710.1		c.54C>A	p.Phe18Leu	missense	Exon 1 of 21	ENSP00000641769.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1200438 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 587062

African (AFR) AF: 0.00 AC: 0 AN: 23864

American (AMR) AF: 0.00 AC: 0 AN: 16442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18484

East Asian (EAS) AF: 0.00 AC: 0 AN: 25698

South Asian (SAS) AF: 0.00 AC: 0 AN: 52872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3364

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 983280

Other (OTH) AF: 0.00 AC: 0 AN: 48352

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	22
DANN	Benign	0.46
DEOGEN2	Benign	0.23	T
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.40	T
PhyloP100		-0.63
PrimateAI	Pathogenic	0.92	D
Sift4G	Pathogenic	0.0	D
PromoterAI		0.16	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.2
Varity_R		0.63
gMVP		0.34
Mutation Taster		=97/3	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-145743115;