7-2257434-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_013321.4(SNX8):​c.1065G>C​(p.Gln355His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

SNX8
NM_013321.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47
Variant links:
Genes affected
SNX8 (HGNC:14972): (sorting nexin 8) Enables identical protein binding activity and phosphatidylinositol binding activity. Involved in early endosome to Golgi transport and intracellular protein transport. Located in early endosome membrane. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]
MIR6836 (HGNC:50067): (microRNA 6836) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40300944).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNX8NM_013321.4 linkc.1065G>C p.Gln355His missense_variant Exon 9 of 11 ENST00000222990.8 NP_037453.1 Q9Y5X2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNX8ENST00000222990.8 linkc.1065G>C p.Gln355His missense_variant Exon 9 of 11 1 NM_013321.4 ENSP00000222990.3 Q9Y5X2
SNX8ENST00000480807.1 linkn.185G>C non_coding_transcript_exon_variant Exon 1 of 3 2
SNX8ENST00000479689.1 linkn.*232G>C downstream_gene_variant 2
MIR6836ENST00000617724.1 linkn.*81G>C downstream_gene_variant 6

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 06, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1065G>C (p.Q355H) alteration is located in exon 9 (coding exon 9) of the SNX8 gene. This alteration results from a G to C substitution at nucleotide position 1065, causing the glutamine (Q) at amino acid position 355 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
Benign
0.25
BayesDel_addAF
Benign
-0.099
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
22
DANN
Benign
0.96
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.49
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.40
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.17
Sift
Uncertain
0.029
D
Sift4G
Benign
0.081
T
Polyphen
0.81
P
Vest4
0.58
MutPred
0.34
Gain of catalytic residue at Q355 (P = 0.0648);
MVP
0.28
MPC
0.73
ClinPred
0.77
D
GERP RS
1.9
Varity_R
0.12
gMVP
0.31

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: chr7-2297069; API