4-173371354-G-A

Variant names:

• chr4-173371354-G-A
• rs773166192
• NM_003864.4:c.172G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003864.4(SAP30):​c.172G>A​(p.Ala58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,486,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: SAP30 NM_003864.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07237545).

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.172G>A	p.Ala58Thr	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.172G>A	p.Ala58Thr	missense	Exon 1 of 4	ENSP00000296504.3	O75446
	SAP30	ENST00000932477.1		c.172G>A	p.Ala58Thr	missense	Exon 1 of 3	ENSP00000602536.1
	SAP30-DT	ENST00000725023.1		n.133+380C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000120 AC: 18 AN: 150378 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000222 AC: 3 AN: 134846 AF XY: 0.0000127

Gnomad AFR exome AF: 0.000355

Gnomad AMR exome AF: 0.0000579

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: 0.00000823 AC: 11 AN: 1336184 Hom.: 0 Cov.: 30 AF XY: 0.00000754 AC XY: 5 AN XY: 663544

African (AFR) AF: 0.000187 AC: 5 AN: 26806

American (AMR) AF: 0.000111 AC: 3 AN: 27102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22082

East Asian (EAS) AF: 0.00 AC: 0 AN: 30836

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 74920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4746

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1060766

Other (OTH) AF: 0.00 AC: 0 AN: 54492

GnomAD4 genome AF: 0.000113 AC: 17 AN: 150486 Hom.: 0 Cov.: 31 AF XY: 0.000109 AC XY: 8 AN XY: 73548

African (AFR) AF: 0.000387 AC: 16 AN: 41324

American (AMR) AF: 0.00 AC: 0 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5084

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67494

Other (OTH) AF: 0.00 AC: 0 AN: 2100

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000132

ExAC AF: 0.0000625 AC: 7

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	0.082
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.62	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.3
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.082
Sift	Benign	0.34	T
Sift4G	Uncertain	0.047	D
Polyphen		0.066	B
Vest4		0.097
MutPred		0.17		Loss of glycosylation at P56 (P = 0.0057)
MVP		0.42
MPC		1.4
ClinPred		0.14	T
GERP RS		4.0
PromoterAI		0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Varity_R		0.11
gMVP		0.32
Mutation Taster		=76/24	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: rs773166192; hg19: chr4-174292505;