chr2-127942513-C-T

Position:

• chr2-127942513-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001330301.2(SAP130):​c.2926G>A​(p.Glu976Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAP130 NM_001330301.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.39

Genes affected

SAP130 (HGNC:29813): (Sin3A associated protein 130) SAP130 is a subunit of the histone deacetylase (see HDAC1; MIM 601241)-dependent SIN3A (MIM 607776) corepressor complex (Fleischer et al., 2003 [PubMed 12724404]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34717363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAP130	NM_001330301.2	c.2926G>A	p.Glu976Lys	missense_variant	20/21	ENST00000643581.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAP130	ENST00000643581.2	c.2926G>A	p.Glu976Lys	missense_variant	20/21		NM_001330301.2	P4
SAP130	ENST00000357702.9	c.3004G>A	p.Glu1002Lys	missense_variant	20/21	1
SAP130	ENST00000259235.7	c.2899G>A	p.Glu967Lys	missense_variant	19/20	1
SAP130	ENST00000259234.10	c.2923G>A	p.Glu975Lys	missense_variant	20/21	5		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2022

The c.3004G>A (p.E1002K) alteration is located in exon 20 (coding exon 20) of the SAP130 gene. This alteration results from a G to A substitution at nucleotide position 3004, causing the glutamic acid (E) at amino acid position 1002 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Pathogenic	1.0
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.6	N;N;.;N
REVEL	Benign	0.26
Sift	Benign	0.046	D;T;.;T
Sift4G	Benign	0.094	T;T;.;T
Polyphen		0.79	.;P;.;.
Vest4		0.39
MutPred		0.43		.;Gain of ubiquitination at E967 (P = 0.0162);.;.;
MVP		0.17
MPC		2.1
ClinPred		0.70	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.68

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-128700087; COSMIC: COSV52104433;