Variant 4-185332650-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001378034.2(SNX25):c.1805A>G(p.Asn602Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

SNX25
NM_001378034.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

Variant links:

Genes affected

SNX25 (HGNC:21883): (sorting nexin 25) Predicted to enable type I transforming growth factor beta receptor binding activity. Involved in negative regulation of pathway-restricted SMAD protein phosphorylation; negative regulation of transforming growth factor beta receptor signaling pathway; and receptor catabolic process. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

SNX25 links:

LOC124900827 (HGNC:):

LOC124900827 links:

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=0.0633426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX25	NM_001378034.2 linkuse as main transcript	c.1805A>G	p.Asn602Ser	missense_variant	10/19	ENST00000652585.2	NP_001364963.1
LOC124900827	XR_007058416.1 linkuse as main transcript	n.172+776T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX25	ENST00000652585.2 linkuse as main transcript	c.1805A>G	p.Asn602Ser	missense_variant	10/19		NM_001378034.2	ENSP00000498676

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

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:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251264

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

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:

0.000106

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000171

AC:

250

AN:

1461802

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

107

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000187

Gnomad4 NFE exome

AF:

0.000216

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000131

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000193

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:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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 submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.1313A>G (p.N438S) alteration is located in exon 10 (coding exon 9) of the SNX25 gene. This alteration results from a A to G substitution at nucleotide position 1313, causing the asparagine (N) at amino acid position 438 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

0.058

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.0052

.;T;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.87

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.81

T;.;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.063

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.6

.;L;L

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.74

.;N;N

REVEL

Benign

0.14

Sift

Benign

0.45

.;T;T

Sift4G

Benign

0.30

T;T;T

Polyphen

0.0010

.;B;B

Vest4

0.17

MVP

0.30

MPC

0.14

ClinPred

0.037

GERP RS

-0.60

Varity_R

0.019

gMVP

0.16

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over