chr7-100572973-G-T

Variant names:

• chr7-100572973-G-T
• rs199499379
• NM_001348680.2:c.398C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001348680.2(SAP25):​c.398C>A​(p.Thr133Lys) 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 pathogenic 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. T133M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49
• Publications: 1 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAP25	NM_001348680.2	c.398C>A	p.Thr133Lys	missense_variant	Exon 4 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3	c.377C>A	p.Thr126Lys	missense_variant	Exon 4 of 6		NP_001162153.2
SAP25	NM_001348677.2	c.104C>A	p.Thr35Lys	missense_variant	Exon 3 of 5		NP_001335606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAP25	ENST00000622764.3	c.398C>A	p.Thr133Lys	missense_variant	Exon 4 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: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.73	.;T;T
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.6	L;.;L
PhyloP100		2.5
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.3	D;.;.
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;.;.
Sift4G	Pathogenic	0.0	D;T;D
Polyphen		1.0	D;.;D
Vest4		0.79
MutPred		0.29		Gain of methylation at T35 (P = 0.0158);.;Gain of methylation at T35 (P = 0.0158);
MVP		0.12
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.68
gMVP		0.38
Mutation Taster		=92/8	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: rs199499379; hg19: chr7-100170596;