Variant chr4-173371378-C-G details in Genebe, Genetics Data Aggregator

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

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]

SAP30 links:

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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	Protein	UniProt
SAP30	NM_003864.4 linkuse as main transcript	c.196C>G	p.Leu66Val	missense_variant	1/4	ENST00000296504.4	NP_003855.1	O75446

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SAP30	ENST00000296504.4 linkuse as main transcript	c.196C>G	p.Leu66Val	missense_variant	1/4	1	NM_003864.4	ENSP00000296504.3		O75446

Frequencies

GnomAD3 genomes

AF:

0.000232

AC:

AN:

151060

Hom.:

Cov.:

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:

AN:

189826

Hom.:

AF XY:

0.000102

AC XY:

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.:

Cov.:

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:

AN:

151060

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

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.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.000233

AC:

ESP6500EA

AF:

0.000360

AC:

ExAC

AF:

0.000102

AC:

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 submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The 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

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.011

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.075

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.21

REVEL

Benign

0.045

Sift

Benign

0.72

Sift4G

Benign

0.69

Polyphen

0.0020

Vest4

0.14

MVP

0.13

MPC

0.64

ClinPred

0.057

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over