13-21146817-C-T

Variant names:

• chr13-21146817-C-T
• rs4620
• NM_005870.5:c.252C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 25 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.012).
• 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	c.252C>T	p.Thr84Thr	synonymous_variant	Exon 3 of 4	ENST00000382533.9	NP_005861.2
SAP18	NM_001366643.2	c.240C>T	p.Thr80Thr	synonymous_variant	Exon 4 of 5		NP_001353572.1
SAP18	NR_172492.1	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	c.252C>T	p.Thr84Thr	synonymous_variant	Exon 3 of 4	1	NM_005870.5	ENSP00000371973.4

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64290 AN: 151694 Hom.: 14838 Cov.: 32

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

GnomAD2 exomes AF: 0.484 AC: 114753 AN: 237200 AF XY: 0.476

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 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.: 32 AF XY: 0.462 AC XY: 330877 AN XY: 716340

African (AFR) AF: 0.249 AC: 8024 AN: 32268

American (AMR) AF: 0.663 AC: 26045 AN: 39308

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 9639 AN: 25244

East Asian (EAS) AF: 0.673 AC: 26586 AN: 39514

South Asian (SAS) AF: 0.413 AC: 34307 AN: 83004

European-Finnish (FIN) AF: 0.521 AC: 27701 AN: 53164

Middle Eastern (MID) AF: 0.376 AC: 2015 AN: 5352

European-Non Finnish (NFE) AF: 0.460 AC: 507460 AN: 1102406

Other (OTH) AF: 0.453 AC: 26882 AN: 59404

GnomAD4 genome AF: 0.424 AC: 64306 AN: 151812 Hom.: 14842 Cov.: 32 AF XY: 0.431 AC XY: 31995 AN XY: 74190

African (AFR) AF: 0.260 AC: 10771 AN: 41358

American (AMR) AF: 0.562 AC: 8571 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1358 AN: 3466

East Asian (EAS) AF: 0.690 AC: 3566 AN: 5170

South Asian (SAS) AF: 0.425 AC: 2050 AN: 4818

European-Finnish (FIN) AF: 0.530 AC: 5570 AN: 10506

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31069 AN: 67934

Other (OTH) AF: 0.434 AC: 915 AN: 2108

Alfa AF: 0.445 Hom.: 10923

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
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4620; hg19: chr13-21720956; COSMIC: COSV66822782;