16-3608599-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_032444.4(SLX4):​c.366G>A​(p.Lys122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLX4
NM_032444.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.492
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 16-3608599-C-T is Benign according to our data. Variant chr16-3608599-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1124203.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.492 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLX4NM_032444.4 linkuse as main transcriptc.366G>A p.Lys122= synonymous_variant 2/15 ENST00000294008.4
SLX4XM_024450471.2 linkuse as main transcriptc.366G>A p.Lys122= synonymous_variant 2/15
SLX4XM_011522715.4 linkuse as main transcriptc.366G>A p.Lys122= synonymous_variant 2/15
SLX4XR_007064923.1 linkuse as main transcriptn.1015G>A non_coding_transcript_exon_variant 2/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLX4ENST00000294008.4 linkuse as main transcriptc.366G>A p.Lys122= synonymous_variant 2/155 NM_032444.4 P1Q8IY92-1
SLX4ENST00000466154.5 linkuse as main transcriptn.661G>A non_coding_transcript_exon_variant 1/71
SLX4ENST00000486524.1 linkuse as main transcriptn.994G>A non_coding_transcript_exon_variant 2/42
SLX4ENST00000697859.1 linkuse as main transcriptn.988G>A non_coding_transcript_exon_variant 2/2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251464
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461882
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
show subpopulations
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:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152162
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Fanconi anemia Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeFeb 29, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
6.1
DANN
Benign
0.74

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

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

Other links and lift over

dbSNP: rs149626570; hg19: chr16-3658600; API