16-29457656-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024044.5(SLX1B):​c.607C>T​(p.Pro203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 15)
Exomes 𝑓: 0.000023 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SLX1B
NM_024044.5 missense

Scores

2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36
Variant links:
Genes affected
SLX1B (HGNC:28748): (SLX1 homolog B, structure-specific endonuclease subunit) This gene encodes a protein that is an important regulator of genome stability. The protein represents the catalytic subunit of the SLX1-SLX4 structure-specific endonuclease, which can resolve DNA secondary structures that are formed during repair and recombination processes. Two identical copies of this gene are located on the p arm of chromosome 16 due to a segmental duplication; this record represents the more telomeric copy. Alternative splicing results in multiple transcript variants. Read-through transcription also occurs between this gene and the downstream SULT1A4 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 4) gene. [provided by RefSeq, Nov 2010]
SLX1B-SULT1A4 (HGNC:48353): (SLX1B-SULT1A4 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring SLX1B (SLX1 structure-specific endonuclease subunit homolog B) and SULT1A4 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 4) genes on the short arm of chromosome 16. A duplicate read-through locus also exists between the SLX1A and SULT1A3 genes located approximately 730 kb downstream on the same chromosome. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.12426537).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLX1BNM_024044.5 linkc.607C>T p.Pro203Ser missense_variant Exon 4 of 6 NP_076949.1 Q9BQ83-1
SLX1BNM_001400286.1 linkc.601C>T p.Pro201Ser missense_variant Exon 4 of 6 NP_001387215.1
SLX1BNM_178044.4 linkc.265C>T p.Pro89Ser missense_variant Exon 3 of 5 NP_835145.1 Q9BQ83-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLX1BENST00000330181.10 linkc.607C>T p.Pro203Ser missense_variant Exon 4 of 6 1 ENSP00000328940.5 Q9BQ83-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
13
AN:
99128
Hom.:
0
Cov.:
15
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00159
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000232
AC:
22
AN:
947198
Hom.:
0
Cov.:
14
AF XY:
0.0000235
AC XY:
11
AN XY:
468134
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000241
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:
0.0000219
Gnomad4 OTH exome
AF:
0.0000247
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000131
AC:
13
AN:
99128
Hom.:
0
Cov.:
15
AF XY:
0.000149
AC XY:
7
AN XY:
46848
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00159
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.607C>T (p.P203S) alteration is located in exon 4 (coding exon 4) of the SLX1B gene. This alteration results from a C to T substitution at nucleotide position 607, causing the proline (P) at amino acid position 203 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
22
DANN
Uncertain
0.98
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-0.95
T
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-2.0
N;N
REVEL
Benign
0.028
Sift
Benign
0.062
T;T
Sift4G
Benign
0.13
T;T
Vest4
0.30
MutPred
0.30
Gain of sheet (P = 0.0344);.;
MVP
0.11
MPC
3.3
ClinPred
0.54
D
GERP RS
2.5
gMVP
0.57

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: rs1371942771; hg19: chr16-29468977; API