chr7-100572502-G-C

Variant names:

• chr7-100572502-G-C
• rs777399353
• NM_001348680.2:c.679C>G

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.679C>G​(p.Pro227Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000781 in 1,280,952 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. 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. P227S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581
• 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=0.05811721).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAP25	NM_001348680.2	c.679C>G	p.Pro227Ala	missense_variant	Exon 6 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3	c.658C>G	p.Pro220Ala	missense_variant	Exon 6 of 6		NP_001162153.2
SAP25	NM_001348677.2	c.385C>G	p.Pro129Ala	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.679C>G	p.Pro227Ala	missense_variant	Exon 6 of 6	5	NM_001348680.2	ENSP00000481773.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.81e-7 AC: 1 AN: 1280952 Hom.: 0 Cov.: 31 AF XY: 0.00000161 AC XY: 1 AN XY: 621134

African (AFR) AF: 0.00 AC: 0 AN: 27890

American (AMR) AF: 0.0000506 AC: 1 AN: 19772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18814

East Asian (EAS) AF: 0.00 AC: 0 AN: 33734

South Asian (SAS) AF: 0.00 AC: 0 AN: 63376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5194

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1028522

Other (OTH) AF: 0.00 AC: 0 AN: 53324

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.9
DANN	Benign	0.55
DEOGEN2	Benign	0.025	T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.30	.;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L;.;L
PhyloP100		-0.58
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.5	N;.;.
REVEL	Benign	0.045
Sift	Benign	0.22	T;.;.
Sift4G	Benign	0.097	T;T;T
Polyphen		0.081	B;.;B
Vest4		0.081
MutPred		0.092		Loss of glycosylation at P129 (P = 0.0143);.;Loss of glycosylation at P129 (P = 0.0143);
MVP		0.014
ClinPred		0.051	T
GERP RS		0.20
Varity_R		0.040
gMVP		0.083
Mutation Taster		=97/3	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: rs777399353; hg19: chr7-100170125;