rs756873295
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_001355436.2(SPTB):c.6724_6726dupATC(p.Ile2242dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SPTB
NM_001355436.2 conservative_inframe_insertion
NM_001355436.2 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.59
Publications
0 publications found
Genes affected
SPTB (HGNC:11274): (spectrin beta, erythrocytic) This locus encodes a member of the spectrin gene family. Spectrin proteins, along with ankyrin, play a role in cell membrane organization and stability. The protein encoded by this locus functions in stability of erythrocyte membranes, and mutations in this gene have been associated with spherocytosis type 2, hereditary elliptocytosis, and neonatal hemolytic anemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]
PLEKHG3 (HGNC:20364): (pleckstrin homology and RhoGEF domain containing G3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of small GTPase mediated signal transduction. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_001355436.2. Strenght limited to Supporting due to length of the change: 1aa.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001355436.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SPTB | NM_001355436.2 | MANE Select | c.6724_6726dupATC | p.Ile2242dup | conservative_inframe_insertion | Exon 34 of 36 | NP_001342365.1 | P11277-2 | |
| PLEKHG3 | NM_001308147.2 | MANE Select | c.*6329_*6331dupATG | 3_prime_UTR | Exon 17 of 17 | NP_001295076.1 | A1L390-1 | ||
| SPTB | NM_001024858.4 | c.6724_6726dupATC | p.Ile2242dup | conservative_inframe_insertion | Exon 33 of 35 | NP_001020029.1 | P11277-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SPTB | ENST00000644917.1 | MANE Select | c.6724_6726dupATC | p.Ile2242dup | conservative_inframe_insertion | Exon 34 of 36 | ENSP00000495909.1 | P11277-2 | |
| SPTB | ENST00000553938.5 | TSL:1 | c.2824_2826dupATC | p.Ile942dup | conservative_inframe_insertion | Exon 16 of 18 | ENSP00000451324.1 | H0YJE6 | |
| PLEKHG3 | ENST00000247226.13 | TSL:1 MANE Select | c.*6329_*6331dupATG | 3_prime_UTR | Exon 17 of 17 | ENSP00000247226.8 | A1L390-1 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 152214Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
0
AN:
152214
Hom.:
Cov.:
32
Gnomad AFR
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GnomAD2 exomes AF: 0.0000159 AC: 4AN: 251478 AF XY: 0.0000221 show subpopulations
GnomAD2 exomes
AF:
AC:
4
AN:
251478
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727244 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1461888
Hom.:
Cov.:
31
AF XY:
AC XY:
4
AN XY:
727244
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1112010
Other (OTH)
AF:
AC:
1
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.415
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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Age
GnomAD4 genome 0.00 AC: 0AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74366
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
152214
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74366
African (AFR)
AF:
AC:
0
AN:
41472
American (AMR)
AF:
AC:
0
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68028
Other (OTH)
AF:
AC:
0
AN:
2094
Alfa
AF:
Hom.:
Bravo
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ClinVar
ClinVar submissions as Germline
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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