5-123001992-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014035.4(SNX24):​c.430C>T​(p.Pro144Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SNX24
NM_014035.4 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.67
Variant links:
Genes affected
SNX24 (HGNC:21533): (sorting nexin 24) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to be involved in protein transport. Predicted to be located in cytoplasmic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNX24NM_014035.4 linkc.430C>T p.Pro144Ser missense_variant Exon 6 of 7 ENST00000261369.9 NP_054754.1 Q9Y343-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNX24ENST00000261369.9 linkc.430C>T p.Pro144Ser missense_variant Exon 6 of 7 1 NM_014035.4 ENSP00000261369.4 Q9Y343-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461586
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727128
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:
0.00
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 27, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.430C>T (p.P144S) alteration is located in exon 6 (coding exon 6) of the SNX24 gene. This alteration results from a C to T substitution at nucleotide position 430, causing the proline (P) at amino acid position 144 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
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.043
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.068
T;.;T;.
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.84
T;.;T;T
M_CAP
Benign
0.024
T
MetaRNN
Uncertain
0.63
D;D;D;D
MetaSVM
Uncertain
-0.28
T
MutationAssessor
Benign
1.6
L;L;.;L
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.8
D;D;D;D
REVEL
Uncertain
0.38
Sift
Benign
0.14
T;T;T;T
Sift4G
Benign
0.11
T;T;T;T
Polyphen
1.0
D;D;.;D
Vest4
0.55
MutPred
0.48
Loss of phosphorylation at Y141 (P = 0.1721);Loss of phosphorylation at Y141 (P = 0.1721);.;Loss of phosphorylation at Y141 (P = 0.1721);
MVP
0.82
MPC
0.53
ClinPred
0.99
D
GERP RS
5.9
Varity_R
0.38
gMVP
0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-122337687; API