chr6-157921522-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_016224.5(SNX9):​c.950-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,609,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

SNX9
NM_016224.5 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.00001756
2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.22
Variant links:
Genes affected
SNX9 (HGNC:14973): (sorting nexin 9) This gene encodes a member of the sorting nexin family. Members of this family contain a phosphoinositide binding domain, and are involved in intracellular trafficking. The encoded protein does not contain a coiled coil region, like some family members, but does contain a SRC homology domain near its N-terminus. The encoded protein is reported to have a variety of interaction partners, including of adaptor protein 2 , dynamin, tyrosine kinase non-receptor 2, Wiskott-Aldrich syndrome-like, and ARP3 actin-related protein 3. The encoded protein is implicated in several stages of intracellular trafficking, including endocytosis, macropinocytosis, and F-actin nucleation. [provided by RefSeq, Jul 2013]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 6-157921522-C-T is Benign according to our data. Variant chr6-157921522-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 742459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNX9NM_016224.5 linkuse as main transcriptc.950-9C>T splice_polypyrimidine_tract_variant, intron_variant ENST00000392185.8 NP_057308.1
SNX9XM_011535886.4 linkuse as main transcriptc.668-9C>T splice_polypyrimidine_tract_variant, intron_variant XP_011534188.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNX9ENST00000392185.8 linkuse as main transcriptc.950-9C>T splice_polypyrimidine_tract_variant, intron_variant 1 NM_016224.5 ENSP00000376024 P1

Frequencies

GnomAD3 genomes
AF:
0.000198
AC:
30
AN:
151556
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000267
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
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:
0.000265
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000132
AC:
33
AN:
249610
Hom.:
0
AF XY:
0.000133
AC XY:
18
AN XY:
134984
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.0000883
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:
0.000221
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000244
AC:
355
AN:
1457800
Hom.:
0
Cov.:
30
AF XY:
0.000239
AC XY:
173
AN XY:
725012
show subpopulations
Gnomad4 AFR exome
AF:
0.000270
Gnomad4 AMR exome
AF:
0.0000683
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000294
Gnomad4 OTH exome
AF:
0.000266
GnomAD4 genome
AF:
0.000198
AC:
30
AN:
151556
Hom.:
0
Cov.:
32
AF XY:
0.000176
AC XY:
13
AN XY:
73932
show subpopulations
Gnomad4 AFR
AF:
0.000267
Gnomad4 AMR
AF:
0.0000657
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000265
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000249
Hom.:
0
Bravo
AF:
0.000215
EpiCase
AF:
0.000493
EpiControl
AF:
0.000238

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 31, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
3.6
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000018
dbscSNV1_RF
Benign
0.0080
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: rs371598888; hg19: chr6-158342554; API