Genetic Variant SAP25:p.Ser183Ser (chr7-100572714-C-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001348680.2(SAP25):c.549G>C(p.Ser183Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,535,728 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 2 hom. )

Consequence

SAP25
NM_001348680.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.31

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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-100572714-C-G is Benign according to our data. Variant chr7-100572714-C-G is described in ClinVar as [Benign]. Clinvar id is 732372.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.31 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SAP25	NM_001348680.2 link	c.549G>C	p.Ser183Ser	synonymous_variant	Exon 5 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3 link	c.528G>C	p.Ser176Ser	synonymous_variant	Exon 5 of 6		NP_001162153.2
SAP25	NM_001348677.2 link	c.255G>C	p.Ser85Ser	synonymous_variant	Exon 4 of 5		NP_001335606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAP25	ENST00000622764.3 link	c.549G>C	p.Ser183Ser	synonymous_variant	Exon 5 of 6	5	NM_001348680.2	ENSP00000481773.2		A0A087WYF9

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

397

AN:

151796

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00911

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.000548

AC:

AN:

138710

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

74382

show subpopulations

Gnomad AFR exome

AF:

0.00910

Gnomad AMR exome

AF:

0.000245

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000240

GnomAD4 exome

AF:

0.000215

AC:

298

AN:

1383814

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

129

AN XY:

682904

show subpopulations

Gnomad4 AFR exome

AF:

0.00779

Gnomad4 AMR exome

AF:

0.000309

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000464

Gnomad4 OTH exome

AF:

0.000622

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

151914

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00908

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000428

Hom.:

Bravo

AF:

0.00288

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 27, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.47

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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