7-100572352-T-C

Variant names:

• chr7-100572352-T-C
• rs575414696
• NM_001348680.2:c.829A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001348680.2(SAP25):​c.829A>G​(p.Ser277Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,373,420 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.827
• Publications: 0 publications found

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]

ENSG00000274272 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015325487).
• BP6: Variant 7-100572352-T-C is Benign according to our data. Variant chr7-100572352-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3316137.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAP25	NM_001348680.2	c.829A>G	p.Ser277Gly	missense_variant	Exon 6 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3	c.808A>G	p.Ser270Gly	missense_variant	Exon 6 of 6		NP_001162153.2
SAP25	NM_001348677.2	c.535A>G	p.Ser179Gly	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	c.829A>G	p.Ser277Gly	missense_variant	Exon 6 of 6	5	NM_001348680.2	ENSP00000481773.2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

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

GnomAD4 exome AF: 0.0000147 AC: 18 AN: 1221124 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 8 AN XY: 587680

African (AFR) AF: 0.00 AC: 0 AN: 25774

American (AMR) AF: 0.00 AC: 0 AN: 13808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17378

East Asian (EAS) AF: 0.000567 AC: 17 AN: 30002

South Asian (SAS) AF: 0.00 AC: 0 AN: 50572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4988

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 998440

Other (OTH) AF: 0.0000198 AC: 1 AN: 50494

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74472

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 14, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.37
DANN	Benign	0.62
DEOGEN2	Benign	0.0020	T;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.33	.;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.015	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.52	N;.;N
PhyloP100		-0.83
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.0	N;.;.
REVEL	Benign	0.034
Sift	Benign	1.0	T;.;.
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.046
MutPred		0.14		Loss of phosphorylation at S179 (P = 0.0048);.;Loss of phosphorylation at S179 (P = 0.0048);
MVP		0.030
ClinPred		0.066	T
GERP RS		-3.4
Varity_R		0.028
gMVP		0.044
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs575414696; hg19: chr7-100169975;