Genetic Variant SAP30:p.Pro55Leu (chr4-173371346-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003864.4(SAP30):c.164C>T(p.Pro55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000741 in 1,457,028 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

SAP30
NM_003864.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04062116).

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.164C>T	p.Pro55Leu	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.164C>T	p.Pro55Leu	missense	Exon 1 of 4	ENSP00000296504.3	O75446
SAP30	ENST00000932477.1		c.164C>T	p.Pro55Leu	missense	Exon 1 of 3	ENSP00000602536.1
SAP30-DT	ENST00000725023.1		n.133+388G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000667

AC:

AN:

150012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000868

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000890

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000159

AC:

AN:

107128

AF XY:

0.000112

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00242

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000395

Gnomad OTH exome

AF:

0.000398

GnomAD4 exome

AF:

0.0000750

AC:

AN:

1307016

Hom.:

Cov.:

AF XY:

0.0000618

AC XY:

AN XY:

647352

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26166

American (AMR)

AF:

0.00

AC:

AN:

23588

Ashkenazi Jewish (ASJ)

AF:

0.00183

AC:

AN:

20740

East Asian (EAS)

AF:

0.00

AC:

AN:

29668

South Asian (SAS)

AF:

0.000112

AC:

AN:

71508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32940

Middle Eastern (MID)

AF:

0.000449

AC:

AN:

4454

European-Non Finnish (NFE)

AF:

0.0000373

AC:

AN:

1044772

Other (OTH)

AF:

0.000207

AC:

AN:

53180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

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

AF:

0.0000667

AC:

AN:

150012

Hom.:

Cov.:

AF XY:

0.0000546

AC XY:

AN XY:

73228

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41092

American (AMR)

AF:

0.00

AC:

AN:

15094

Ashkenazi Jewish (ASJ)

AF:

0.000868

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000890

AC:

AN:

67428

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.000236

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000558

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

Benign

0.079

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.55

PhyloP100

3.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.86

REVEL

Benign

0.047

Sift

Uncertain

0.0070

Sift4G

Benign

0.12

Polyphen

0.16

Vest4

0.32

MutPred

0.18

Loss of glycosylation at P56 (P = 0.0057)

MVP

0.32

MPC

1.4

ClinPred

0.21

GERP RS

3.1

PromoterAI

-0.087

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.55

Mutation Taster

=88/12

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over