rs763110999

Variant names:

• chr7-100572911-C-T
• rs763110999
• NM_001348680.2:c.460G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001348680.2(SAP25):​c.460G>A​(p.Val154Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,477,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.252
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032161772).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348680.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAP25	NM_001348680.2	MANE Select	c.460G>A	p.Val154Met	missense	Exon 4 of 6	NP_001335609.1	A0A087WYF9
	SAP25	NM_001168682.3		c.439G>A	p.Val147Met	missense	Exon 4 of 6	NP_001162153.2
	SAP25	NM_001348677.2		c.166G>A	p.Val56Met	missense	Exon 3 of 5	NP_001335606.1	Q8TEE9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAP25	ENST00000622764.3	TSL:5 MANE Select	c.460G>A	p.Val154Met	missense	Exon 4 of 6	ENSP00000481773.2	A0A087WYF9
	SAP25	ENST00000538735.5	TSL:3	c.166G>A	p.Val56Met	missense	Exon 4 of 6	ENSP00000442339.1	Q8TEE9
	SAP25	ENST00000614631.4	TSL:2	c.166G>A	p.Val56Met	missense	Exon 3 of 5	ENSP00000481351.1	Q8TEE9

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 151980 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000642 AC: 6 AN: 93492 AF XY: 0.0000611

Gnomad AFR exome AF: 0.000292

Gnomad AMR exome AF: 0.000192

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.0000219 AC: 29 AN: 1325196 Hom.: 0 Cov.: 32 AF XY: 0.0000231 AC XY: 15 AN XY: 648426

African (AFR) AF: 0.000238 AC: 7 AN: 29352

American (AMR) AF: 0.000155 AC: 4 AN: 25804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35186

South Asian (SAS) AF: 0.00 AC: 0 AN: 71266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32238

Middle Eastern (MID) AF: 0.000185 AC: 1 AN: 5398

European-Non Finnish (NFE) AF: 0.0000114 AC: 12 AN: 1049666

Other (OTH) AF: 0.0000907 AC: 5 AN: 55104

GnomAD4 genome AF: 0.0000921 AC: 14 AN: 151980 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74248

African (AFR) AF: 0.000169 AC: 7 AN: 41370

American (AMR) AF: 0.000262 AC: 4 AN: 15272

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

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000174 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000900 AC: 2

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.8
DANN	Benign	0.70
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.25
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.049
Sift	Benign	0.32	T
Sift4G	Benign	0.12	T
Polyphen		0.65	P
Vest4		0.13
MutPred		0.17		Loss of sheet (P = 0.0457)
MVP		0.014
ClinPred		0.032	T
GERP RS		0.95
Varity_R		0.029
gMVP		0.025
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs763110999; hg19: chr7-100170534;