NM_001348680.2:c.688G>A

Variant names:

• chr7-100572493-C-T
• rs540582443
• NM_001348680.2:c.688G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_001348680.2(SAP25):​c.688G>A​(p.Gly230Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,431,608 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 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.952
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08336851).
• BP6: Variant 7-100572493-C-T is Benign according to our data. Variant chr7-100572493-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3437308.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.688G>A	p.Gly230Ser	missense_variant	Exon 6 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3	c.667G>A	p.Gly223Ser	missense_variant	Exon 6 of 6		NP_001162153.2
SAP25	NM_001348677.2	c.394G>A	p.Gly132Ser	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.688G>A	p.Gly230Ser	missense_variant	Exon 6 of 6	5	NM_001348680.2	ENSP00000481773.2

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152116 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000478

GnomAD2 exomes AF: 0.00 AC: 0 AN: 58402 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 AF: 0.0000133 AC: 17 AN: 1279374 Hom.: 0 Cov.: 32 AF XY: 0.0000129 AC XY: 8 AN XY: 620222

African (AFR) AF: 0.000540 AC: 15 AN: 27782

American (AMR) AF: 0.00 AC: 0 AN: 19484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18732

East Asian (EAS) AF: 0.00 AC: 0 AN: 33598

South Asian (SAS) AF: 0.00 AC: 0 AN: 63120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5176

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1027934

Other (OTH) AF: 0.0000376 AC: 2 AN: 53260

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74432

African (AFR) AF: 0.000650 AC: 27 AN: 41538

American (AMR) AF: 0.000131 AC: 2 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000272

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 05, 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	0.11
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.1
DANN	Benign	0.76
DEOGEN2	Benign	0.029	T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.41	.;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.083	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;L
PhyloP100		-0.95
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N;.;.
REVEL	Benign	0.021
Sift	Benign	0.17	T;.;.
Sift4G	Benign	0.31	T;T;T
Polyphen		0.29	B;.;B
Vest4		0.11
MutPred		0.18		Loss of catalytic residue at G132 (P = 0.0013);.;Loss of catalytic residue at G132 (P = 0.0013);
MVP		0.014
ClinPred		0.14	T
GERP RS		2.3
Varity_R		0.047
gMVP		0.091
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs540582443; hg19: chr7-100170116;