rs201192909

Positions:

• chr16-3602235-C-A
• chr16-3602235-C-T

Variant summary

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

The NM_032444.4(SLX4):​c.833G>T​(p.Arg278Leu) 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 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLX4 NM_032444.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.266

Genes affected

SLX4 (HGNC:23845): (SLX4 structure-specific endonuclease subunit) This gene encodes a protein that functions as an assembly component of multiple structure-specific endonucleases. These endonuclease complexes are required for repair of specific types of DNA lesions and critical for cellular responses to replication fork failure. Mutations in this gene were found in patients with Fanconi anemia. [provided by RefSeq, Sep 2016]

SLX4 (HGNC:):

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=0.12479329).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4	c.833G>T	p.Arg278Leu	missense_variant	4/15	ENST00000294008.4	NP_115820.2
SLX4	XM_024450471.2	c.833G>T	p.Arg278Leu	missense_variant	4/15		XP_024306239.1
SLX4	XM_011522715.4	c.833G>T	p.Arg278Leu	missense_variant	4/15		XP_011521017.1
SLX4	XR_007064923.1	n.1482G>T		non_coding_transcript_exon_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4	c.833G>T	p.Arg278Leu	missense_variant	4/15	5	NM_032444.4	ENSP00000294008.3
SLX4	ENST00000466154.5	n.1128G>T		non_coding_transcript_exon_variant	3/7	1
SLX4	ENST00000486524.1	n.1461G>T		non_coding_transcript_exon_variant	4/4	2
SLX4	ENST00000697858.1	n.174G>T		non_coding_transcript_exon_variant	2/3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727216

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: 8.99e-7

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	0.12
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.45	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.048
Sift	Benign	0.030	D
Sift4G	Uncertain	0.045	D
Polyphen		0.015	B
Vest4		0.22
MutPred		0.36		Loss of solvent accessibility (P = 0.0299);
MVP		0.11
MPC		0.067
ClinPred		0.18	T
GERP RS		-5.4
Varity_R		0.055
gMVP		0.16

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-3652236;