dbSNP rs1237625115: SAP25:p.Pro141Leu (chr7-100572949-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001348680.2(SAP25):c.422C>T(p.Pro141Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000295 in 1,356,668 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SAP25
NM_001348680.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SAP25	NM_001348680.2 link	c.422C>T	p.Pro141Leu	missense_variant	Exon 4 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3 link	c.401C>T	p.Pro134Leu	missense_variant	Exon 4 of 6		NP_001162153.2
SAP25	NM_001348677.2 link	c.128C>T	p.Pro43Leu	missense_variant	Exon 3 of 5		NP_001335606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAP25	ENST00000622764.3 link	c.422C>T	p.Pro141Leu	missense_variant	Exon 4 of 6	5	NM_001348680.2	ENSP00000481773.2		A0A087WYF9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000842

AC:

AN:

118774

AF XY:

0.00

show subpopulations

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

AF:

0.00000295

AC:

AN:

1356668

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

667172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30666

American (AMR)

AF:

0.00

AC:

AN:

31722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23196

East Asian (EAS)

AF:

0.00

AC:

AN:

35480

South Asian (SAS)

AF:

0.0000132

AC:

AN:

75872

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5548

European-Non Finnish (NFE)

AF:

0.00000282

AC:

AN:

1064116

Other (OTH)

AF:

0.00

AC:

AN:

56512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.128C>T (p.P43L) alteration is located in exon 4 (coding exon 2) of the SAP25 gene. This alteration results from a C to T substitution at nucleotide position 128, causing the proline (P) at amino acid position 43 to be replaced by a leucine (L). 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

0.31

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

T;.;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.70

.;T;T

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.61

D;D;D

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.6

L;.;L

PhyloP100

2.2

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-8.7

D;.;.

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.66

MutPred

0.37

Loss of loop (P = 0.0073);.;Loss of loop (P = 0.0073);

MVP

0.25

ClinPred

0.99

GERP RS

5.4

Varity_R

0.68

gMVP

0.32

Mutation Taster

=85/15

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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rs1237625115

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over