chr16-3582334-T-C

Variant names:

• chr16-3582334-T-C
• rs3751839
• NM_032444.4:c.*8A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032444.4(SLX4):​c.*8A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 1,607,746 control chromosomes in the GnomAD database, including 4,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (567 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3457 hom.)
• Consequence: SLX4 NM_032444.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.90
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group P

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000261938 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-3582334-T-C is Benign according to our data. Variant chr16-3582334-T-C is described in ClinVar as Benign. ClinVar VariationId is 262029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032444.4. 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
	SLX4	NM_032444.4	MANE Select	c.*8A>G		3_prime_UTR	Exon 15 of 15	NP_115820.2	Q8IY92-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX4	ENST00000294008.4	TSL:5 MANE Select	c.*8A>G		3_prime_UTR	Exon 15 of 15	ENSP00000294008.3	Q8IY92-1
	ENSG00000261938	ENST00000573982.1	TSL:3	n.199-802T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12362 AN: 152080 Hom.: 564 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.0827

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.0606

Gnomad FIN AF: 0.0856

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0676

Gnomad OTH AF: 0.0790

GnomAD2 exomes AF: 0.0681 AC: 16743 AN: 245926 AF XY: 0.0657

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.0782

Gnomad ASJ exome AF: 0.0235

Gnomad EAS exome AF: 0.0357

Gnomad FIN exome AF: 0.0863

Gnomad NFE exome AF: 0.0676

Gnomad OTH exome AF: 0.0573

GnomAD4 exome AF: 0.0665 AC: 96732 AN: 1455548 Hom.: 3457 Cov.: 32 AF XY: 0.0658 AC XY: 47643 AN XY: 724214

African (AFR) AF: 0.112 AC: 3728 AN: 33390

American (AMR) AF: 0.0748 AC: 3342 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0227 AC: 594 AN: 26118

East Asian (EAS) AF: 0.0320 AC: 1268 AN: 39678

South Asian (SAS) AF: 0.0609 AC: 5245 AN: 86114

European-Finnish (FIN) AF: 0.0823 AC: 4155 AN: 50494

Middle Eastern (MID) AF: 0.0523 AC: 219 AN: 4190

European-Non Finnish (NFE) AF: 0.0668 AC: 74204 AN: 1110724

Other (OTH) AF: 0.0661 AC: 3977 AN: 60142

GnomAD4 genome AF: 0.0813 AC: 12377 AN: 152198 Hom.: 567 Cov.: 32 AF XY: 0.0810 AC XY: 6029 AN XY: 74414

African (AFR) AF: 0.115 AC: 4757 AN: 41528

American (AMR) AF: 0.0824 AC: 1260 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 78 AN: 3470

East Asian (EAS) AF: 0.0362 AC: 187 AN: 5170

South Asian (SAS) AF: 0.0611 AC: 295 AN: 4830

European-Finnish (FIN) AF: 0.0856 AC: 907 AN: 10594

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0676 AC: 4598 AN: 68002

Other (OTH) AF: 0.0773 AC: 163 AN: 2110

Alfa AF: 0.0692 Hom.: 227

Bravo AF: 0.0827

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Fanconi anemia complementation group P (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.026
DANN	Benign	0.25
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3751839; hg19: chr16-3632335;