13-21140599-G-C

Variant names:

• chr13-21140599-G-C
• rs570548873
• NM_005870.5:c.47G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005870.5(SAP18):​c.47G>C​(p.Arg16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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. R16H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SAP18 NM_005870.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 3 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]

ENSG00000302602 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13220441).

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.47G>C	p.Arg16Pro	missense	Exon 1 of 4	NP_005861.2	O00422-2
	SAP18	NM_001366643.2		c.-159G>C		5_prime_UTR	Exon 1 of 5	NP_001353572.1
	SAP18	NR_172492.1		n.481G>C		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAP18	ENST00000382533.9	TSL:1 MANE Select	c.47G>C	p.Arg16Pro	missense	Exon 1 of 4	ENSP00000371973.4	O00422-2
	SAP18	ENST00000621421.4	TSL:1	c.47G>C	p.Arg16Pro	missense	Exon 1 of 4	ENSP00000481842.1	O00422-2
	SAP18	ENST00000607003.5	TSL:1	c.-11G>C		5_prime_UTR	Exon 1 of 4	ENSP00000475925.1	O00422-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244628 AF XY: 0.00

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: 0.00000908

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458620 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725384

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.00 AC: 0 AN: 85716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110508

Other (OTH) AF: 0.00 AC: 0 AN: 60234

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.88
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.37
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.013
Sift	Benign	0.064	T
Sift4G	Benign	0.19	T
Vest4		0.43
MutPred		0.22		Loss of helix (P = 0.0138)
MVP		0.49
MPC		0.00064
ClinPred		0.097	T
GERP RS		0.75
PromoterAI		-0.058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.49
Mutation Taster		=88/12	polymorphism

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: rs570548873; hg19: chr13-21714738;