13-21140578-A-G

Variant names:

• chr13-21140578-A-G
• rs530592109
• NM_005870.5:c.26A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005870.5(SAP18):​c.26A>G​(p.Gln9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,605,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: SAP18 NM_005870.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.40
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.081736535).
• BS2: High AC in GnomAd4 at 7 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAP18	NM_005870.5	MANE Select	c.26A>G	p.Gln9Arg	missense	Exon 1 of 4	NP_005861.2	O00422-2
	SAP18	NM_001366643.2		c.-180A>G		5_prime_UTR	Exon 1 of 5	NP_001353572.1
	SAP18	NR_172492.1		n.460A>G		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.26A>G	p.Gln9Arg	missense	Exon 1 of 4	ENSP00000371973.4	O00422-2
	SAP18	ENST00000621421.4	TSL:1	c.26A>G	p.Gln9Arg	missense	Exon 1 of 4	ENSP00000481842.1	O00422-2
	SAP18	ENST00000607003.5	TSL:1	c.-32A>G		5_prime_UTR	Exon 1 of 4	ENSP00000475925.1	O00422-1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000938 AC: 22 AN: 234520 AF XY: 0.0000866

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000604

Gnomad ASJ exome AF: 0.00113

Gnomad EAS exome AF: 0.0000578

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000763

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000337 AC: 49 AN: 1452914 Hom.: 0 Cov.: 31 AF XY: 0.0000416 AC XY: 30 AN XY: 721976

African (AFR) AF: 0.0000301 AC: 1 AN: 33176

American (AMR) AF: 0.0000230 AC: 1 AN: 43508

Ashkenazi Jewish (ASJ) AF: 0.000925 AC: 24 AN: 25934

East Asian (EAS) AF: 0.0000768 AC: 3 AN: 39064

South Asian (SAS) AF: 0.00 AC: 0 AN: 84856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52674

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1107932

Other (OTH) AF: 0.0000167 AC: 1 AN: 60008

GnomAD4 genome AF: 0.0000459 AC: 7 AN: 152354 Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41600

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000158 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000907 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.4
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.041
Sift	Benign	0.15	T
Sift4G	Benign	0.50	T
Vest4		0.48
MutPred		0.20		Gain of methylation at Q9 (P = 0.0036)
MVP		0.72
MPC		0.00071
ClinPred		0.25	T
GERP RS		5.4
PromoterAI		-0.063	Neutral
gMVP		0.30
Mutation Taster		=95/5	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: rs530592109; hg19: chr13-21714717;