Genetic Variant SAP25:p.Gly283Val (chr7-100572333-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001348680.2(SAP25):c.848G>T(p.Gly283Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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. G283D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SAP25
NM_001348680.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.260

Publications

0 publications found

Variant links:

Genes affected

SAP25 (HGNC:41908): (Sin3A associated protein 25) Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SAP25 links:

ENSG00000274272 (HGNC:):

ENSG00000274272 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06700978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SAP25	NM_001348680.2 link	c.848G>T	p.Gly283Val	missense_variant	Exon 6 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3 link	c.827G>T	p.Gly276Val	missense_variant	Exon 6 of 6		NP_001162153.2
SAP25	NM_001348677.2 link	c.554G>T	p.Gly185Val	missense_variant	Exon 5 of 5		NP_001335606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAP25	ENST00000622764.3 link	c.848G>T	p.Gly283Val	missense_variant	Exon 6 of 6	5	NM_001348680.2	ENSP00000481773.2		A0A087WYF9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

32750

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1208022

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

580382

African (AFR)

AF:

0.00

AC:

AN:

25400

American (AMR)

AF:

0.00

AC:

AN:

13050

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17062

East Asian (EAS)

AF:

0.00

AC:

AN:

29422

South Asian (SAS)

AF:

0.00

AC:

AN:

47552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4978

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

991524

Other (OTH)

AF:

0.00

AC:

AN:

49892

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.5

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.024

T;.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.37

.;T;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.067

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;L

PhyloP100

-0.26

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.6

N;.;.

REVEL

Benign

0.029

Sift

Benign

0.18

T;.;.

Sift4G

Benign

0.15

T;T;T

Polyphen

0.037

B;.;B

Vest4

0.065

MutPred

0.12

Loss of relative solvent accessibility (P = 0.0306);.;Loss of relative solvent accessibility (P = 0.0306);

MVP

0.055

ClinPred

0.15

GERP RS

2.3

Varity_R

0.087

gMVP

0.048

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over