chr3-125476734-C-T

Variant summary

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

The NM_003794.4(SNX4):​c.749G>A​(p.Gly250Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000208 in 1,445,558 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SNX4
NM_003794.4 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.49
Variant links:
Genes affected
SNX4 (HGNC:11175): (sorting nexin 4) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein associated with the long isoform of the leptin receptor and with receptor tyrosine kinases for platelet-derived growth factor, insulin, and epidermal growth factor in cell cultures, but its function is unknown. This protein may form oligomeric complexes with family members. Two transcript variants, one protein coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Nov 2012]

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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
SNX4NM_003794.4 linkc.749G>A p.Gly250Asp missense_variant Exon 8 of 14 ENST00000251775.9 NP_003785.1 O95219-1
SNX4XM_017007414.3 linkc.749G>A p.Gly250Asp missense_variant Exon 8 of 15 XP_016862903.1
SNX4NR_073435.2 linkn.657G>A non_coding_transcript_exon_variant Exon 7 of 13

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNX4ENST00000251775.9 linkc.749G>A p.Gly250Asp missense_variant Exon 8 of 14 1 NM_003794.4 ENSP00000251775.4 O95219-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000405
AC:
1
AN:
247046
Hom.:
0
AF XY:
0.00000749
AC XY:
1
AN XY:
133500
show subpopulations
Gnomad AFR exome
AF:
0.0000624
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000208
AC:
3
AN:
1445558
Hom.:
0
Cov.:
26
AF XY:
0.00000139
AC XY:
1
AN XY:
719798
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
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:
0.00000182
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 28, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.749G>A (p.G250D) alteration is located in exon 8 (coding exon 8) of the SNX4 gene. This alteration results from a G to A substitution at nucleotide position 749, causing the glycine (G) at amino acid position 250 to be replaced by an aspartic acid (D). 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
0.96
BayesDel_addAF
Uncertain
0.050
T
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.086
T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.029
D
MetaRNN
Uncertain
0.71
D
MetaSVM
Benign
-0.51
T
MutationAssessor
Benign
2.0
M
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
-0.95
N
REVEL
Benign
0.16
Sift
Benign
0.15
T
Sift4G
Uncertain
0.037
D
Polyphen
0.99
D
Vest4
0.90
MutPred
0.40
Loss of MoRF binding (P = 0.0725);
MVP
0.78
MPC
0.30
ClinPred
0.29
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.29
gMVP
0.81

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: rs1416426710; hg19: chr3-125195578; API