chr4-173371321-G-T

Variant names:

• chr4-173371321-G-T
• rs184876228
• NM_003864.4:c.139G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003864.4(SAP30):​c.139G>T​(p.Ala47Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00573 in 1,313,746 control chromosomes in the GnomAD database, including 393 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. A47T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.013 (71 hom., cov: 31)
  • Exomes 𝑓: 0.0048 (322 hom.)
• Consequence: SAP30 NM_003864.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.865
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003619641).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

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.139G>T	p.Ala47Ser	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.139G>T	p.Ala47Ser	missense	Exon 1 of 4	ENSP00000296504.3	O75446
	SAP30	ENST00000932477.1		c.139G>T	p.Ala47Ser	missense	Exon 1 of 3	ENSP00000602536.1
	SAP30-DT	ENST00000725023.1		n.133+413C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1942 AN: 149768 Hom.: 70 Cov.: 31

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0575

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0967

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.00407

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000445

Gnomad OTH AF: 0.0213

GnomAD2 exomes AF: 0.0273 AC: 189 AN: 6912 AF XY: 0.0243

Gnomad AFR exome AF: 0.0230

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00169

Gnomad OTH exome AF: 0.0236

GnomAD4 exome AF: 0.00479 AC: 5570 AN: 1163868 Hom.: 322 Cov.: 30 AF XY: 0.00486 AC XY: 2754 AN XY: 566926

African (AFR) AF: 0.00942 AC: 209 AN: 22176

American (AMR) AF: 0.0919 AC: 750 AN: 8164

Ashkenazi Jewish (ASJ) AF: 0.0000704 AC: 1 AN: 14212

East Asian (EAS) AF: 0.130 AC: 3153 AN: 24298

South Asian (SAS) AF: 0.0111 AC: 529 AN: 47864

European-Finnish (FIN) AF: 0.00331 AC: 85 AN: 25706

Middle Eastern (MID) AF: 0.00336 AC: 11 AN: 3274

European-Non Finnish (NFE) AF: 0.000219 AC: 213 AN: 971824

Other (OTH) AF: 0.0134 AC: 619 AN: 46350

GnomAD4 genome AF: 0.0130 AC: 1952 AN: 149878 Hom.: 71 Cov.: 31 AF XY: 0.0140 AC XY: 1021 AN XY: 73190

African (AFR) AF: 0.0105 AC: 434 AN: 41254

American (AMR) AF: 0.0574 AC: 865 AN: 15068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.0966 AC: 489 AN: 5060

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4824

European-Finnish (FIN) AF: 0.00407 AC: 39 AN: 9588

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000446 AC: 30 AN: 67338

Other (OTH) AF: 0.0244 AC: 51 AN: 2086

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.0198

ExAC AF: 0.0160 AC: 527

Asia WGS AF: 0.0550 AC: 188 AN: 3420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.86
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.26	N
REVEL	Benign	0.027
Sift	Benign	0.70	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.035
MPC		1.1
ClinPred		0.0088	T
GERP RS		1.8
PromoterAI		0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.033
gMVP		0.30
Mutation Taster		=97/3	polymorphism (auto)

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: rs184876228; hg19: chr4-174292472;