Genetic Variant SAP25:p.Asp270Glu (chr7-100572371-G-T) – 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.810C>A(p.Asp270Glu) 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. Variant has been reported in ClinVar 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

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.06

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=0.048233032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SAP25	NM_001348680.2 link	c.810C>A	p.Asp270Glu	missense_variant	Exon 6 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3 link	c.789C>A	p.Asp263Glu	missense_variant	Exon 6 of 6		NP_001162153.2
SAP25	NM_001348677.2 link	c.516C>A	p.Asp172Glu	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.810C>A	p.Asp270Glu	missense_variant	Exon 6 of 6	5	NM_001348680.2	ENSP00000481773.2		A0A087WYF9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1243692

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

599972

African (AFR)

AF:

0.00

AC:

AN:

26576

American (AMR)

AF:

0.00

AC:

AN:

15322

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17872

East Asian (EAS)

AF:

0.00

AC:

AN:

31248

South Asian (SAS)

AF:

0.00

AC:

AN:

55516

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4948

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1010360

Other (OTH)

AF:

0.00

AC:

AN:

51536

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 03, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.516C>A (p.D172E) alteration is located in exon 6 (coding exon 4) of the SAP25 gene. This alteration results from a C to A substitution at nucleotide position 516, causing the aspartic acid (D) at amino acid position 172 to be replaced by a glutamic acid (E). 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

0.17

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.29

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.013

T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.31

.;T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;.;L

PhyloP100

-1.1

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.94

N;.;.

REVEL

Benign

0.0080

Sift

Benign

0.68

T;.;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0070

B;.;B

Vest4

0.034

MutPred

0.11

Gain of glycosylation at P174 (P = 0.0714);.;Gain of glycosylation at P174 (P = 0.0714);

MVP

0.014

ClinPred

0.047

GERP RS

-3.2

Varity_R

0.083

gMVP

0.037

Mutation Taster

=99/1

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over