Genetic Variant SAP30:p.Pro6Ala (chr4-173371198-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003864.4(SAP30):c.16C>G(p.Pro6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P6S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

SAP30
NM_003864.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.32

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:

SAP30-DT (HGNC:54424): (SAP30 divergent transcript)

SAP30-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16964552).

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.16C>G	p.Pro6Ala	missense	Exon 1 of 4	NP_003855.1	O75446

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAP30	ENST00000296504.4	TSL:1 MANE Select	c.16C>G	p.Pro6Ala	missense	Exon 1 of 4	ENSP00000296504.3	O75446
SAP30	ENST00000932477.1		c.16C>G	p.Pro6Ala	missense	Exon 1 of 3	ENSP00000602536.1
SAP30	ENST00000504618.1	TSL:3	n.376C>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151486

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151486

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73962

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41386

American (AMR)

AF:

0.00

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67736

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

PhyloP100

2.3

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.78

REVEL

Benign

0.084

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.054

Polyphen

0.0020

Vest4

0.17

MutPred

0.15

Gain of glycosylation at T5 (P = 0.0328)

MVP

0.30

MPC

1.1

ClinPred

0.64

GERP RS

3.7

PromoterAI

0.028

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.22

gMVP

0.73

Mutation Taster

=76/24

polymorphism

(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