NM_001348680.2:c.767G>C

Variant names:

• chr7-100572414-C-G
• NM_001348680.2:c.767G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001348680.2(SAP25):​c.767G>C​(p.Arg256Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.527
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06568971).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAP25	NM_001348680.2	c.767G>C	p.Arg256Thr	missense_variant	Exon 6 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3	c.746G>C	p.Arg249Thr	missense_variant	Exon 6 of 6		NP_001162153.2
SAP25	NM_001348677.2	c.473G>C	p.Arg158Thr	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.767G>C	p.Arg256Thr	missense_variant	Exon 6 of 6	5	NM_001348680.2	ENSP00000481773.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.473G>C (p.R158T) alteration is located in exon 6 (coding exon 4) of the SAP25 gene. This alteration results from a G to C substitution at nucleotide position 473, causing the arginine (R) at amino acid position 158 to be replaced by a threonine (T). 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	0.18
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.036	T;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.57	.;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.066	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.;L
PhyloP100		0.53
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.7	D;.;.
REVEL	Benign	0.049
Sift	Benign	0.24	T;.;.
Sift4G	Benign	0.37	T;T;T
Polyphen		0.046	B;.;B
Vest4		0.15
MutPred		0.13		Gain of phosphorylation at R158 (P = 0.0088);.;Gain of phosphorylation at R158 (P = 0.0088);
MVP		0.014
ClinPred		0.35	T
GERP RS		1.9
Varity_R		0.12
gMVP		0.23
Mutation Taster		=100/0	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

hg19: chr7-100170037;