Genetic Variant SAP18:p.Thr84Thr (chr13-21146817-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_005870.5(SAP18):c.252C>T(p.Thr84Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,591,476 control chromosomes in the GnomAD database, including 174,008 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 14842 hom., cov: 32)

Exomes 𝑓: 0.46 ( 159166 hom. )

Consequence

SAP18
NM_005870.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP7

Synonymous conserved (PhyloP=-2.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAP18	NM_005870.5 link	c.252C>T	p.Thr84Thr	synonymous_variant	Exon 3 of 4	ENST00000382533.9	NP_005861.2	O00422-2
SAP18	NM_001366643.2 link	c.240C>T	p.Thr80Thr	synonymous_variant	Exon 4 of 5		NP_001353572.1
SAP18	NR_172492.1 link	n.674-369C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAP18	ENST00000382533.9 link	c.252C>T	p.Thr84Thr	synonymous_variant	Exon 3 of 4	1	NM_005870.5	ENSP00000371973.4		O00422-2

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64290

AN:

151694

Hom.:

14838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.261

Gnomad AMI

AF:

0.371

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.690

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.439

GnomAD3 exomes

AF:

0.484

AC:

114753

AN:

237200

Hom.:

29512

AF XY:

0.476

AC XY:

61177

AN XY:

128546

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.675

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.682

Gnomad SAS exome

AF:

0.415

Gnomad FIN exome

AF:

0.522

Gnomad NFE exome

AF:

0.453

Gnomad OTH exome

AF:

0.484

GnomAD4 exome

AF:

0.464

AC:

668659

AN:

1439664

Hom.:

159166

Cov.:

AF XY:

0.462

AC XY:

330877

AN XY:

716340

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.663

Gnomad4 ASJ exome

AF:

0.382

Gnomad4 EAS exome

AF:

0.673

Gnomad4 SAS exome

AF:

0.413

Gnomad4 FIN exome

AF:

0.521

Gnomad4 NFE exome

AF:

0.460

Gnomad4 OTH exome

AF:

0.453

GnomAD4 genome

AF:

0.424

AC:

64306

AN:

151812

Hom.:

14842

Cov.:

AF XY:

0.431

AC XY:

31995

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.260

Gnomad4 AMR

AF:

0.562

Gnomad4 ASJ

AF:

0.392

Gnomad4 EAS

AF:

0.690

Gnomad4 SAS

AF:

0.425

Gnomad4 FIN

AF:

0.530

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.434

Alfa

AF:

0.445

Hom.:

9811

Bravo

AF:

0.422

Asia WGS

AF:

0.528

AC:

1833

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

5.5

DANN

Benign

0.56

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over