16-3598074-G-C

Position:

• chr16-3598074-G-C

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.1164-75C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0623 in 1,561,208 control chromosomes in the GnomAD database, including 3,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (292 hom., cov: 33)
  • Exomes 𝑓: 0.063 (2968 hom.)
• Consequence: SLX4 NM_032444.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.497

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=-0.88).
• BP6: Variant 16-3598074-G-C is Benign according to our data. Variant chr16-3598074-G-C is described in ClinVar as [Benign]. Clinvar id is 1250198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4	c.1164-75C>G		intron_variant		ENST00000294008.4	NP_115820.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4	c.1164-75C>G		intron_variant		5	NM_032444.4	ENSP00000294008	P1
SLX4	ENST00000466154.5	n.2385-75C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0591 AC: 8998 AN: 152190 Hom.: 292 Cov.: 33

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0364

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.0865

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.0549

GnomAD4 exome AF: 0.0626 AC: 88200 AN: 1408900 Hom.: 2968 AF XY: 0.0620 AC XY: 43614 AN XY: 703794

Gnomad4 AFR exome AF: 0.0426

Gnomad4 AMR exome AF: 0.0676

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.0315

Gnomad4 SAS exome AF: 0.0533

Gnomad4 FIN exome AF: 0.0832

Gnomad4 NFE exome AF: 0.0654

Gnomad4 OTH exome AF: 0.0580

GnomAD4 genome AF: 0.0591 AC: 8996 AN: 152308 Hom.: 292 Cov.: 33 AF XY: 0.0605 AC XY: 4505 AN XY: 74470

Gnomad4 AFR AF: 0.0436

Gnomad4 AMR AF: 0.0713

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.0363

Gnomad4 SAS AF: 0.0537

Gnomad4 FIN AF: 0.0865

Gnomad4 NFE AF: 0.0656

Gnomad4 OTH AF: 0.0543

Alfa AF: 0.0316 Hom.: 17

Bravo AF: 0.0574

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
DANN	Benign	0.45

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

LitVar

Other links and lift over

dbSNP: rs59622164; hg19: chr16-3648075;