20-45833923-C-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_033421.4(SNX21):c.4C>G(p.His2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SNX21
NM_033421.4 missense
NM_033421.4 missense
Scores
3
1
14
Clinical Significance
Conservation
PhyloP100: 2.76
Publications
0 publications found
Genes affected
SNX21 (HGNC:16154): (sorting nexin family member 21) 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 does not contain a coiled coil region, like some family members. The specific function of this protein has not been determined. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
TNNC2 (HGNC:11944): (troponin C2, fast skeletal type) Troponin (Tn), a key protein complex in the regulation of striated muscle contraction, is composed of 3 subunits. The Tn-I subunit inhibits actomyosin ATPase, the Tn-T subunit binds tropomyosin and Tn-C, while the Tn-C subunit binds calcium and overcomes the inhibitory action of the troponin complex on actin filaments. The protein encoded by this gene is the Tn-C subunit. [provided by RefSeq, Jul 2008]
TNNC2 Gene-Disease associations (from GenCC):
- congenital myopathy 15Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
- hypertrophic cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14240718).
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_033421.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SNX21 | TSL:1 MANE Select | c.4C>G | p.His2Asp | missense | Exon 1 of 4 | ENSP00000418593.1 | Q969T3-1 | ||
| SNX21 | TSL:1 | c.4C>G | p.His2Asp | missense | Exon 1 of 5 | ENSP00000344586.5 | Q969T3-2 | ||
| SNX21 | TSL:1 | c.4C>G | p.His2Asp | missense | Exon 1 of 5 | ENSP00000420169.1 | Q969T3-3 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152190
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00 AC: 0AN: 49914 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
49914
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
AF:
Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1274426Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 624146
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1274426
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
624146
African (AFR)
AF:
AC:
0
AN:
24580
American (AMR)
AF:
AC:
0
AN:
15848
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19090
East Asian (EAS)
AF:
AC:
0
AN:
29554
South Asian (SAS)
AF:
AC:
0
AN:
59960
European-Finnish (FIN)
AF:
AC:
0
AN:
44404
Middle Eastern (MID)
AF:
AC:
0
AN:
4140
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1024792
Other (OTH)
AF:
AC:
0
AN:
52058
GnomAD4 genome 0.00000657 AC: 1AN: 152304Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74462 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152304
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74462
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41574
American (AMR)
AF:
AC:
0
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5174
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68008
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ExAC
AF:
AC:
1
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
B
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.0275)
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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