chr7-100572715-G-C

Variant names:

• chr7-100572715-G-C
• rs556504446
• NM_001348680.2:c.548C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001348680.2(SAP25):​c.548C>G​(p.Ser183Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S183L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAP25	NM_001348680.2	c.548C>G	p.Ser183Trp	missense_variant	Exon 5 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3	c.527C>G	p.Ser176Trp	missense_variant	Exon 5 of 6		NP_001162153.2
SAP25	NM_001348677.2	c.254C>G	p.Ser85Trp	missense_variant	Exon 4 of 5		NP_001335606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAP25	ENST00000622764.3	c.548C>G	p.Ser183Trp	missense_variant	Exon 5 of 6	5	NM_001348680.2	ENSP00000481773.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;.;T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.79	.;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.;L
PhyloP100		0.10
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.2	D;.;.
REVEL	Benign	0.081
Sift	Benign	0.039	D;.;.
Sift4G	Uncertain	0.031	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.66
MutPred		0.33		Loss of disorder (P = 0.0112);.;Loss of disorder (P = 0.0112);
MVP		0.055
ClinPred		0.80	D
GERP RS		-2.0
Varity_R		0.072
gMVP		0.18
Mutation Taster		=99/1	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: rs556504446; hg19: chr7-100170338;