NM_003864.4:c.62C>A

Variant names:

• chr4-173371244-C-A
• rs1216814236
• NM_003864.4:c.62C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003864.4(SAP30):​c.62C>A​(p.Ala21Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000807 in 1,239,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A21V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: SAP30 NM_003864.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26930022).

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.62C>A	p.Ala21Glu	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.62C>A	p.Ala21Glu	missense	Exon 1 of 4	ENSP00000296504.3	O75446
	SAP30	ENST00000932477.1		c.62C>A	p.Ala21Glu	missense	Exon 1 of 3	ENSP00000602536.1
	SAP30-DT	ENST00000725023.1		n.133+490G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.07e-7 AC: 1 AN: 1239700 Hom.: 0 Cov.: 30 AF XY: 0.00000163 AC XY: 1 AN XY: 612428

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24468

American (AMR) AF: 0.0000658 AC: 1 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19962

East Asian (EAS) AF: 0.00 AC: 0 AN: 26494

South Asian (SAS) AF: 0.00 AC: 0 AN: 64854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3478

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1006374

Other (OTH) AF: 0.00 AC: 0 AN: 49402

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.7
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	0.11	N
REVEL	Benign	0.099
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.20	B
Vest4		0.28
MutPred		0.31		Gain of relative solvent accessibility (P = 0.09)
MVP		0.34
MPC		1.3
ClinPred		0.67	D
GERP RS		4.1
PromoterAI		-0.032	Neutral
Varity_R		0.38
gMVP		0.75
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: rs1216814236; hg19: chr4-174292395;