Genetic Variant SAP18:p.Gln9Pro (chr13-21140578-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005870.5(SAP18):c.26A>C(p.Gln9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 1,605,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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. Q9R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SAP18
NM_005870.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.40

Publications

0 publications found

Variant links:

Genes affected

SAP18 (HGNC:10530): (Sin3A associated protein 18) 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, SAP30, HDAC1, HDAC2, RbAp46, RbAp48, and other polypeptides. This protein directly interacts with SIN3 and enhances SIN3-mediated transcriptional repression when tethered to the promoter. A pseudogene has been identified on chromosome 2. [provided by RefSeq, Dec 2008]

SAP18 links:

ENSG00000302602 (HGNC:):

ENSG00000302602 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2066763).

BS2

High AC in GnomAdExome4 at 38 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005870.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAP18	NM_005870.5	MANE Select	c.26A>C	p.Gln9Pro	missense	Exon 1 of 4	NP_005861.2	O00422-2
SAP18	NM_001366643.2		c.-180A>C		5_prime_UTR	Exon 1 of 5	NP_001353572.1
SAP18	NR_172492.1		n.460A>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAP18	ENST00000382533.9	TSL:1 MANE Select	c.26A>C	p.Gln9Pro	missense	Exon 1 of 4	ENSP00000371973.4	O00422-2
SAP18	ENST00000621421.4	TSL:1	c.26A>C	p.Gln9Pro	missense	Exon 1 of 4	ENSP00000481842.1	O00422-2
SAP18	ENST00000607003.5	TSL:1	c.-32A>C		5_prime_UTR	Exon 1 of 4	ENSP00000475925.1	O00422-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000426

AC:

AN:

234520

AF XY:

0.0000709

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000262

AC:

AN:

1452914

Hom.:

Cov.:

AF XY:

0.0000360

AC XY:

AN XY:

721976

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33176

American (AMR)

AF:

0.00

AC:

AN:

43508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25934

East Asian (EAS)

AF:

0.00

AC:

AN:

39064

South Asian (SAS)

AF:

0.000389

AC:

AN:

84856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52674

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107932

Other (OTH)

AF:

0.0000833

AC:

AN:

60008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

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:

0.00000656

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41600

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.0000495

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.98

PhyloP100

3.4

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.26

REVEL

Benign

0.051

Sift

Benign

0.068

Sift4G

Benign

0.13

Vest4

0.41

MutPred

0.12

Gain of methylation at R12 (P = 0.0602)

MVP

0.68

MPC

0.00067

ClinPred

0.29

GERP RS

5.4

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.33

Mutation Taster

=84/16

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

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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