20-10622700-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001009608.3(SLX4IP):​c.548C>T​(p.Ser183Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SLX4IP
NM_001009608.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37
Variant links:
Genes affected
SLX4IP (HGNC:16225): (SLX4 interacting protein)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06586471).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLX4IPNM_001009608.3 linkuse as main transcriptc.548C>T p.Ser183Leu missense_variant 8/8 ENST00000334534.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLX4IPENST00000334534.10 linkuse as main transcriptc.548C>T p.Ser183Leu missense_variant 8/81 NM_001009608.3 P1
SLX4IPENST00000488816.1 linkuse as main transcriptc.168-13596C>T intron_variant, NMD_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152070
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000240
AC:
6
AN:
249966
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135156
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1460724
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
726604
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00000360
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152070
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.0000966
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 07, 2023The c.548C>T (p.S183L) alteration is located in exon 8 (coding exon 7) of the SLX4IP gene. This alteration results from a C to T substitution at nucleotide position 548, causing the serine (S) at amino acid position 183 to be replaced by a leucine (L). 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
AlphaMissense
Benign
0.099
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.098
T
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.20
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.066
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-2.5
D
REVEL
Benign
0.082
Sift
Benign
0.10
T
Sift4G
Uncertain
0.016
D
Polyphen
0.12
B
Vest4
0.093
MVP
0.46
MPC
0.35
ClinPred
0.21
T
GERP RS
4.8
Varity_R
0.17
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs138545867; hg19: chr20-10603348; API