4-173371315-C-A

Variant names:

• chr4-173371315-C-A
• rs1392487218
• NM_003864.4:c.133C>A

Variant summary

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

The NM_003864.4(SAP30):​c.133C>A​(p.Pro45Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,302,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P45Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SAP30 NM_003864.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.266
• Publications: 0 publications found

Genes affected

SAP30 (HGNC:10532): (Sin3A associated protein 30) 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, SAP18, HDAC1, HDAC2, RbAp46, RbAp48, and other polypeptides. This complex is active in deacetylating core histone octamers, but inactive in deacetylating nucleosomal histones. A pseudogene of this gene is located on chromosome 3. [provided by RefSeq, Jul 2008]

SAP30-DT (HGNC:54424): (SAP30 divergent transcript)

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=0.14425609).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003864.4. 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
	SAP30	NM_003864.4	MANE Select	c.133C>A	p.Pro45Thr	missense	Exon 1 of 4	NP_003855.1	O75446

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAP30	ENST00000296504.4	TSL:1 MANE Select	c.133C>A	p.Pro45Thr	missense	Exon 1 of 4	ENSP00000296504.3	O75446
	SAP30	ENST00000932477.1		c.133C>A	p.Pro45Thr	missense	Exon 1 of 3	ENSP00000602536.1
	SAP30-DT	ENST00000725023.1		n.133+419G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 149478 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000298

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 4536 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000139 AC: 16 AN: 1152944 Hom.: 0 Cov.: 30 AF XY: 0.00000714 AC XY: 4 AN XY: 560604

African (AFR) AF: 0.00 AC: 0 AN: 21912

American (AMR) AF: 0.00 AC: 0 AN: 7766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13926

East Asian (EAS) AF: 0.00 AC: 0 AN: 23922

South Asian (SAS) AF: 0.00 AC: 0 AN: 45868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3174

European-Non Finnish (NFE) AF: 0.0000145 AC: 14 AN: 965476

Other (OTH) AF: 0.0000436 AC: 2 AN: 45824

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 149478 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 72956

African (AFR) AF: 0.00 AC: 0 AN: 41058

American (AMR) AF: 0.00 AC: 0 AN: 15042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5070

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000298 AC: 2 AN: 67216

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.00 Hom.: 0

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	0.071
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.27
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.030
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.072	T
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.21		Gain of sheet (P = 0.0101)
MVP		0.21
MPC		1.3
ClinPred		0.16	T
GERP RS		2.0
PromoterAI		0.073	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.29
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1392487218; hg19: chr4-174292466;