7-100572468-C-T

Variant names:

• chr7-100572468-C-T
• rs1217395885
• NM_001348680.2:c.713G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001348680.2(SAP25):​c.713G>A​(p.Gly238Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 1,277,306 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.366

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06595582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAP25	NM_001348680.2	c.713G>A	p.Gly238Glu	missense_variant	Exon 6 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3	c.692G>A	p.Gly231Glu	missense_variant	Exon 6 of 6		NP_001162153.2
SAP25	NM_001348677.2	c.419G>A	p.Gly140Glu	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.713G>A	p.Gly238Glu	missense_variant	Exon 6 of 6	5	NM_001348680.2	ENSP00000481773.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000172 AC: 1 AN: 58170 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 28698

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000157 AC: 2 AN: 1277306 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 618732

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000525

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000188

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.419G>A (p.G140E) alteration is located in exon 6 (coding exon 4) of the SAP25 gene. This alteration results from a G to A substitution at nucleotide position 419, causing the glycine (G) at amino acid position 140 to be replaced by a glutamic acid (E). 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	0.29
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T;.;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.67	.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.066	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.0	D;.;.
REVEL	Benign	0.12
Sift	Benign	0.58	T;.;.
Sift4G	Benign	0.38	T;T;T
Polyphen		0.48	P;.;P
Vest4		0.13
MutPred		0.050		Loss of glycosylation at S139 (P = 0.0505);.;Loss of glycosylation at S139 (P = 0.0505);
MVP		0.061
ClinPred		0.34	T
GERP RS		3.6
Varity_R		0.13
gMVP		0.10

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

Publications

LitVar

Other links and lift over

dbSNP: rs1217395885; hg19: chr7-100170091;