rs199499379

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001348680.2(SAP25):​c.398C>T​(p.Thr133Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000171 in 1,508,526 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000080 ( 1 hom. )

Consequence

SAP25
NM_001348680.2 missense

Scores

4
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

Publications

1 publications found
Variant links:
Genes affected
SAP25 (HGNC:41908): (Sin3A associated protein 25) Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.08828694).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SAP25NM_001348680.2 linkc.398C>T p.Thr133Met missense_variant Exon 4 of 6 ENST00000622764.3 NP_001335609.1
SAP25NM_001168682.3 linkc.377C>T p.Thr126Met missense_variant Exon 4 of 6 NP_001162153.2
SAP25NM_001348677.2 linkc.104C>T p.Thr35Met missense_variant Exon 3 of 5 NP_001335606.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SAP25ENST00000622764.3 linkc.398C>T p.Thr133Met missense_variant Exon 4 of 6 5 NM_001348680.2 ENSP00000481773.2 A0A087WYF9

Frequencies

GnomAD3 genomes
AF:
0.000960
AC:
146
AN:
152056
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00336
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000252
AC:
30
AN:
119072
AF XY:
0.000174
show subpopulations
Gnomad AFR exome
AF:
0.00299
Gnomad AMR exome
AF:
0.000193
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000283
GnomAD4 exome
AF:
0.0000796
AC:
108
AN:
1356352
Hom.:
1
Cov.:
32
AF XY:
0.0000585
AC XY:
39
AN XY:
666978
show subpopulations
African (AFR)
AF:
0.00241
AC:
74
AN:
30660
American (AMR)
AF:
0.000191
AC:
6
AN:
31446
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23180
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35478
South Asian (SAS)
AF:
0.000105
AC:
8
AN:
75952
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33784
Middle Eastern (MID)
AF:
0.000180
AC:
1
AN:
5550
European-Non Finnish (NFE)
AF:
0.00000564
AC:
6
AN:
1063808
Other (OTH)
AF:
0.000230
AC:
13
AN:
56494
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.479
Heterozygous variant carriers
0
7
14
21
28
35
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000986
AC:
150
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.000901
AC XY:
67
AN XY:
74402
show subpopulations
African (AFR)
AF:
0.00345
AC:
143
AN:
41498
American (AMR)
AF:
0.000392
AC:
6
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5168
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67960
Other (OTH)
AF:
0.00
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
8
16
24
32
40
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000542
Hom.:
0
Bravo
AF:
0.00100
ExAC
AF:
0.000207
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 27, 2021
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.104C>T (p.T35M) alteration is located in exon 4 (coding exon 2) of the SAP25 gene. This alteration results from a C to T substitution at nucleotide position 104, causing the threonine (T) at amino acid position 35 to be replaced by a methionine (M). 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.15
T;.;T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.84
.;T;T
MetaRNN
Benign
0.088
T;T;T
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
1.6
L;.;L
PhyloP100
2.5
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-5.0
D;.;.
REVEL
Benign
0.19
Sift
Pathogenic
0.0
D;.;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.71
MutPred
0.33
Loss of phosphorylation at T35 (P = 0.0334);.;Loss of phosphorylation at T35 (P = 0.0334);
MVP
0.12
ClinPred
0.13
T
GERP RS
4.5
Varity_R
0.29
gMVP
0.30
Mutation Taster
=90/10
polymorphism

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

Other links and lift over

dbSNP: rs199499379; hg19: chr7-100170596; API