NM_001009608.3:c.52G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001009608.3(SLX4IP):​c.52G>C​(p.Asp18His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SLX4IP
NM_001009608.3 missense

Scores

8
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11
Variant links:
Genes affected
SLX4IP (HGNC:16225): (SLX4 interacting protein)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.86

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLX4IPNM_001009608.3 linkc.52G>C p.Asp18His missense_variant Exon 3 of 8 ENST00000334534.10 NP_001009608.1 Q5VYV7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLX4IPENST00000334534.10 linkc.52G>C p.Asp18His missense_variant Exon 3 of 8 1 NM_001009608.3 ENSP00000335557.5 Q5VYV7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 18, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.52G>C (p.D18H) alteration is located in exon 3 (coding exon 2) of the SLX4IP gene. This alteration results from a G to C substitution at nucleotide position 52, causing the aspartic acid (D) at amino acid position 18 to be replaced by a histidine (H). 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
Pathogenic
0.85
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T
Eigen
Pathogenic
0.80
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.032
D
MetaRNN
Pathogenic
0.86
D
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-6.2
D
REVEL
Uncertain
0.53
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.97
MutPred
0.61
Gain of sheet (P = 0.1208);
MVP
0.52
MPC
0.52
ClinPred
1.0
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.93
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-10536903; API