rs80116508

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032444.4(SLX4):c.1163+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 1,611,776 control chromosomes in the GnomAD database, including 3,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 358 hom., cov: 31)

Exomes 𝑓: 0.063 ( 3131 hom. )

Consequence

SLX4
NM_032444.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.330

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 16-3600969-G-A is Benign according to our data. Variant chr16-3600969-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3600969-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4 linkuse as main transcript	c.1163+10C>T		intron_variant		ENST00000294008.4	NP_115820.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 linkuse as main transcript	c.1163+10C>T	intron_variant		5	NM_032444.4	ENSP00000294008	P1	Q8IY92-1
SLX4	ENST00000466154.5 linkuse as main transcript	n.2384+10C>T	intron_variant, non_coding_transcript_variant		1
SLX4	ENST00000486524.1 linkuse as main transcript	n.2727C>T	non_coding_transcript_exon_variant	4/4	2
SLX4	ENST00000697858.1 linkuse as main transcript	n.514C>T	non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.0669

AC:

10167

AN:

151930

Hom.:

357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0705

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0757

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0367

Gnomad SAS

AF:

0.0528

Gnomad FIN

AF:

0.0867

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0656

Gnomad OTH

AF:

0.0598

GnomAD3 exomes

AF:

0.0621

AC:

15459

AN:

249084

Hom.:

545

AF XY:

0.0607

AC XY:

8189

AN XY:

135004

show subpopulations

Gnomad AFR exome

AF:

0.0705

Gnomad AMR exome

AF:

0.0717

Gnomad ASJ exome

AF:

0.0188

Gnomad EAS exome

AF:

0.0349

Gnomad SAS exome

AF:

0.0521

Gnomad FIN exome

AF:

0.0869

Gnomad NFE exome

AF:

0.0647

Gnomad OTH exome

AF:

0.0518

GnomAD4 exome

AF:

0.0631

AC:

92103

AN:

1459728

Hom.:

3131

Cov.:

AF XY:

0.0623

AC XY:

45265

AN XY:

726222

show subpopulations

Gnomad4 AFR exome

AF:

0.0722

Gnomad4 AMR exome

AF:

0.0690

Gnomad4 ASJ exome

AF:

0.0188

Gnomad4 EAS exome

AF:

0.0319

Gnomad4 SAS exome

AF:

0.0533

Gnomad4 FIN exome

AF:

0.0829

Gnomad4 NFE exome

AF:

0.0649

Gnomad4 OTH exome

AF:

0.0602

GnomAD4 genome

AF:

0.0669

AC:

10176

AN:

152048

Hom.:

358

Cov.:

AF XY:

0.0678

AC XY:

5039

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0705

Gnomad4 AMR

AF:

0.0754

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0366

Gnomad4 SAS

AF:

0.0537

Gnomad4 FIN

AF:

0.0867

Gnomad4 NFE

AF:

0.0656

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0460

Hom.:

Bravo

AF:

0.0668

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 28, 2016	- -
Likely benign, no assertion criteria provided	curation	Leiden Open Variation Database	Aug 31, 2012	Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -

Fanconi anemia complementation group P

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Sep 23, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.19

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over