NM_001348680.2:c.575G>T

Variant names:

• chr7-100572688-C-A
• rs1236434638
• NM_001348680.2:c.575G>T

Variant summary

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

The NM_001348680.2(SAP25):​c.575G>T​(p.Arg192Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,734 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R192C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• 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.575G>T	p.Arg192Leu	missense_variant	Exon 5 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3	c.554G>T	p.Arg185Leu	missense_variant	Exon 5 of 6		NP_001162153.2
SAP25	NM_001348677.2	c.281G>T	p.Arg94Leu	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.575G>T	p.Arg192Leu	missense_variant	Exon 5 of 6	5	NM_001348680.2	ENSP00000481773.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383734 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 682882

African (AFR) AF: 0.00 AC: 0 AN: 31570

American (AMR) AF: 0.00 AC: 0 AN: 35592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25134

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 79214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078454

Other (OTH) AF: 0.00 AC: 0 AN: 57868

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.78	.;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	L;.;L
PhyloP100		2.2
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.5	D;.;.
REVEL	Benign	0.21
Sift	Uncertain	0.0080	D;.;.
Sift4G	Pathogenic	0.0	D;T;D
Polyphen		1.0	D;.;D
Vest4		0.64
MutPred		0.45		Loss of solvent accessibility (P = 0.0079);.;Loss of solvent accessibility (P = 0.0079);
MVP		0.19
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.49
gMVP		0.40
Mutation Taster		=94/6	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: rs1236434638; hg19: chr7-100170311; COSMIC: COSV55711275; COSMIC: COSV55711275;