Genetic Variant NM_003864.4:c.430G>C (chr4-173373504-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003864.4(SAP30):c.430G>C(p.Asp144His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,453,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SAP30
NM_003864.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.86

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32259098).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003864.4. 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
	SAP30	NM_003864.4	MANE Select	c.430G>C	p.Asp144His	missense	Exon 2 of 4	NP_003855.1	O75446

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAP30	ENST00000296504.4	TSL:1 MANE Select	c.430G>C	p.Asp144His	missense	Exon 2 of 4	ENSP00000296504.3	O75446
	SAP30	ENST00000932477.1		c.430G>C	p.Asp144His	missense	Exon 2 of 3	ENSP00000602536.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

244852

AF XY:

0.00000755

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000123

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:

0.00

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1453806

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33080

American (AMR)

AF:

0.0000919

AC:

AN:

43508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25838

East Asian (EAS)

AF:

0.00

AC:

AN:

39260

South Asian (SAS)

AF:

0.00

AC:

AN:

84984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108264

Other (OTH)

AF:

0.0000167

AC:

AN:

60016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.015

MetaRNN

Benign

0.32

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

2.0

PhyloP100

9.9

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.24

Sift

Uncertain

0.022

Sift4G

Uncertain

0.038

Polyphen

1.0

Vest4

0.26

MutPred

0.32

Loss of disorder (P = 0.1073)

MVP

0.63

MPC

1.8

ClinPred

0.97

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.46

Mutation Taster

=46/54

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over