13-21146817-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005870.5(SAP18):​c.252C>G​(p.Thr84Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.032).
• BP7: Synonymous conserved (PhyloP=-2.08 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAP18	NM_005870.5	MANE Select	c.252C>G	p.Thr84Thr	synonymous	Exon 3 of 4	NP_005861.2
	SAP18	NM_001366643.2		c.240C>G	p.Thr80Thr	synonymous	Exon 4 of 5	NP_001353572.1
	SAP18	NR_172492.1		n.674-369C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAP18	ENST00000382533.9	TSL:1 MANE Select	c.252C>G	p.Thr84Thr	synonymous	Exon 3 of 4	ENSP00000371973.4
	SAP18	ENST00000621421.4	TSL:1	c.252C>G	p.Thr84Thr	synonymous	Exon 3 of 4	ENSP00000481842.1
	SAP18	ENST00000607003.5	TSL:1	c.195C>G	p.Thr65Thr	synonymous	Exon 3 of 4	ENSP00000475925.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1444082 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 718376

African (AFR) AF: 0.00 AC: 0 AN: 32328

American (AMR) AF: 0.00 AC: 0 AN: 39362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25282

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.00 AC: 0 AN: 83140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5364

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106296

Other (OTH) AF: 0.00 AC: 0 AN: 59570

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.0
DANN	Benign	0.69
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;