chr16-3600969-G-A

Position:

• chr16-3600969-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.330

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]

ACMG classification

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	c.1163+10C>T		intron_variant		ENST00000294008.4	NP_115820.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0669 AC: 10167 AN: 151930 Hom.: 357 Cov.: 31

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

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.: 31 AF XY: 0.0623 AC XY: 45265 AN XY: 726222

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.: 31 AF XY: 0.0678 AC XY: 5039 AN XY: 74316

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.: 72

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

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

Other links and lift over

dbSNP: rs80116508; hg19: chr16-3650970; COSMIC: COSV53561020;