rs1382425995

Variant names:

• chr7-100572309-G-A
• rs1382425995
• NM_001348680.2:c.872C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-100572309-G-A
• chr7-100572309-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001348680.2(SAP25):​c.872C>T​(p.Thr291Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0500
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12341508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAP25	NM_001348680.2	c.872C>T	p.Thr291Ile	missense_variant	Exon 6 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3	c.851C>T	p.Thr284Ile	missense_variant	Exon 6 of 6		NP_001162153.2
SAP25	NM_001348677.2	c.578C>T	p.Thr193Ile	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.872C>T	p.Thr291Ile	missense_variant	Exon 6 of 6	5	NM_001348680.2	ENSP00000481773.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1177746 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 563600

African (AFR) AF: 0.00 AC: 0 AN: 24588

American (AMR) AF: 0.00 AC: 0 AN: 11808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16346

East Asian (EAS) AF: 0.00 AC: 0 AN: 28202

South Asian (SAS) AF: 0.00 AC: 0 AN: 40778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4896

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 974868

Other (OTH) AF: 0.00 AC: 0 AN: 48578

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.578C>T (p.T193I) alteration is located in exon 6 (coding exon 4) of the SAP25 gene. This alteration results from a C to T substitution at nucleotide position 578, causing the threonine (T) at amino acid position 193 to be replaced by an isoleucine (I). 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	0.15
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T;.;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.45	.;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;L
PhyloP100		0.050
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.1	D;.;.
REVEL	Benign	0.075
Sift	Uncertain	0.015	D;.;.
Sift4G	Uncertain	0.055	T;T;T
Polyphen		0.66	P;.;P
Vest4		0.10
MutPred		0.082		Loss of phosphorylation at T193 (P = 0.023);.;Loss of phosphorylation at T193 (P = 0.023);
MVP		0.040
ClinPred		0.82	D
GERP RS		-0.12
Varity_R		0.11
gMVP		0.14
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1382425995; hg19: chr7-100169932;