Variant chr2-127950385-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001330301.2(SAP130):c.2446A>G(p.Thr816Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,614,110 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SAP130
NM_001330301.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0990

Variant links:

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]

SAP130 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059300184).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SAP130	NM_001330301.2 linkuse as main transcript	c.2446A>G	p.Thr816Ala	missense_variant	17/21	ENST00000643581.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAP130	ENST00000643581.2 linkuse as main transcript	c.2446A>G	p.Thr816Ala	missense_variant	17/21		NM_001330301.2	P4
SAP130	ENST00000357702.9 linkuse as main transcript	c.2524A>G	p.Thr842Ala	missense_variant	17/21	1			Q9H0E3-3
SAP130	ENST00000259235.7 linkuse as main transcript	c.2419A>G	p.Thr807Ala	missense_variant	16/20	1			Q9H0E3-1
SAP130	ENST00000259234.10 linkuse as main transcript	c.2443A>G	p.Thr815Ala	missense_variant	17/21	5		A1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000384

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.2524A>G (p.T842A) alteration is located in exon 17 (coding exon 17) of the SAP130 gene. This alteration results from a A to G substitution at nucleotide position 2524, causing the threonine (T) at amino acid position 842 to be replaced by an alanine (A). 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

Benign

0.067

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.059

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.79

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

N;N;.;N

REVEL

Benign

0.048

Sift

Benign

0.19

T;T;.;T

Sift4G

Benign

0.22

T;T;.;T

Polyphen

0.0

.;B;.;.

Vest4

0.13

MutPred

0.099

.;Loss of glycosylation at T807 (P = 0.0087);.;.;

MVP

0.21

MPC

0.44

ClinPred

0.079

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over