7-100572569-C-T

Variant names:

Variant summary

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

The NM_001348680.2(SAP25):c.612G>A(p.Met204Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000395 in 152,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SAP25
NM_001348680.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.176

Publications

2 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: 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=0.030749172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SAP25	NM_001348680.2 link	c.612G>A	p.Met204Ile	missense_variant, splice_region_variant	Exon 6 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3 link	c.591G>A	p.Met197Ile	missense_variant, splice_region_variant	Exon 6 of 6		NP_001162153.2
SAP25	NM_001348677.2 link	c.318G>A	p.Met106Ile	missense_variant, splice_region_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.612G>A	p.Met204Ile	missense_variant, splice_region_variant	Exon 6 of 6	5	NM_001348680.2	ENSP00000481773.2		A0A087WYF9

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

78226

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:

1304418

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

636348

African (AFR)

AF:

0.00

AC:

AN:

28386

American (AMR)

AF:

0.00

AC:

AN:

22508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20034

East Asian (EAS)

AF:

0.00

AC:

AN:

33944

South Asian (SAS)

AF:

0.00

AC:

AN:

68040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1040264

Other (OTH)

AF:

0.00

AC:

AN:

54218

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2092

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

Asia WGS

AF:

0.000289

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

May 15, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.318G>A (p.M106I) alteration is located in exon 6 (coding exon 4) of the SAP25 gene. This alteration results from a G to A substitution at nucleotide position 318, causing the methionine (M) at amino acid position 106 to be replaced by an isoleucine (I). 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

0.25

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.8

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0081

T;.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.63

.;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.031

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N

PhyloP100

-0.18

PrimateAI

Benign

0.31

PROVEAN

Benign

0.10

N;.;.

REVEL

Benign

0.073

Sift

Benign

0.090

T;.;.

Sift4G

Benign

0.13

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.033

MutPred

0.13

Gain of methylation at K111 (P = 0.1184);.;Gain of methylation at K111 (P = 0.1184);

MVP

0.030

ClinPred

0.043

GERP RS

-1.4

Varity_R

0.079

gMVP

0.070

Mutation Taster

=97/3

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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7-100572569-C-T

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