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GeneBe

4-173371378-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003864.4(SAP30):c.196C>G(p.Leu66Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,557,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

SAP30
NM_003864.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.730
Variant links:
Genes affected
SAP30 (HGNC:10532): (Sin3A associated protein 30) Histone acetylation plays a key role in the regulation of eukaryotic gene expression. Histone acetylation and deacetylation are catalyzed by multisubunit complexes. The protein encoded by this gene is a component of the histone deacetylase complex, which includes SIN3, SAP18, HDAC1, HDAC2, RbAp46, RbAp48, and other polypeptides. This complex is active in deacetylating core histone octamers, but inactive in deacetylating nucleosomal histones. A pseudogene of this gene is located on chromosome 3. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07490784).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SAP30NM_003864.4 linkuse as main transcriptc.196C>G p.Leu66Val missense_variant 1/4 ENST00000296504.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SAP30ENST00000296504.4 linkuse as main transcriptc.196C>G p.Leu66Val missense_variant 1/41 NM_003864.4 P1

Frequencies

GnomAD3 genomes
AF:
0.000232
AC:
35
AN:
151060
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000484
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000658
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:
0.000458
Gnomad OTH
AF:
0.000482
GnomAD3 exomes
AF:
0.000105
AC:
20
AN:
189826
Hom.:
0
AF XY:
0.000102
AC XY:
11
AN XY:
107710
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000335
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:
0.000220
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000262
AC:
369
AN:
1406838
Hom.:
0
Cov.:
31
AF XY:
0.000265
AC XY:
186
AN XY:
700650
show subpopulations
Gnomad4 AFR exome
AF:
0.0000682
Gnomad4 AMR exome
AF:
0.0000245
Gnomad4 ASJ exome
AF:
0.0000406
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000330
Gnomad4 OTH exome
AF:
0.0000687
GnomAD4 genome
AF:
0.000232
AC:
35
AN:
151060
Hom.:
0
Cov.:
31
AF XY:
0.000136
AC XY:
10
AN XY:
73778
show subpopulations
Gnomad4 AFR
AF:
0.0000484
Gnomad4 AMR
AF:
0.0000658
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000458
Gnomad4 OTH
AF:
0.000482
Alfa
AF:
0.000261
Hom.:
0
Bravo
AF:
0.000253
ESP6500AA
AF:
0.000233
AC:
1
ESP6500EA
AF:
0.000360
AC:
3
ExAC
AF:
0.000102
AC:
12

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 submitterclinical testingAmbry GeneticsSep 17, 2021The c.196C>G (p.L66V) alteration is located in exon 1 (coding exon 1) of the SAP30 gene. This alteration results from a C to G substitution at nucleotide position 196, causing the leucine (L) at amino acid position 66 to be replaced by a valine (V). 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
0.085
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.49
Cadd
Benign
17
Dann
Benign
0.64
DEOGEN2
Benign
0.011
T
Eigen
Benign
-0.97
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.33
N
LIST_S2
Benign
0.77
T
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.075
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
N
MutationTaster
Benign
0.87
D
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
0.21
N
REVEL
Benign
0.045
Sift
Benign
0.72
T
Sift4G
Benign
0.69
T
Polyphen
0.0020
B
Vest4
0.14
MVP
0.13
MPC
0.64
ClinPred
0.057
T
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.062
gMVP
0.27

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.

Other links and lift over

dbSNP: rs201052655; hg19: chr4-174292529; API