7-100572740-C-T

Variant names:

• chr7-100572740-C-T
• rs777260933
• NM_001348680.2:c.523G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001348680.2(SAP25):​c.523G>A​(p.Val175Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. V175L) 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: -1.91
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03230861).

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.523G>A	p.Val175Met	missense	Exon 5 of 6	NP_001335609.1	A0A087WYF9
	SAP25	NM_001168682.3		c.502G>A	p.Val168Met	missense	Exon 5 of 6	NP_001162153.2
	SAP25	NM_001348677.2		c.229G>A	p.Val77Met	missense	Exon 4 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.523G>A	p.Val175Met	missense	Exon 5 of 6	ENSP00000481773.2	A0A087WYF9
	SAP25	ENST00000538735.5	TSL:3	c.229G>A	p.Val77Met	missense	Exon 5 of 6	ENSP00000442339.1	Q8TEE9
	SAP25	ENST00000614631.4	TSL:2	c.229G>A	p.Val77Met	missense	Exon 4 of 5	ENSP00000481351.1	Q8TEE9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000732 AC: 1 AN: 136686 AF XY: 0.0000136

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381776 Hom.: 0 Cov.: 32 AF XY: 0.00000147 AC XY: 1 AN XY: 682090

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31326

American (AMR) AF: 0.00 AC: 0 AN: 34756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24998

East Asian (EAS) AF: 0.00 AC: 0 AN: 35722

South Asian (SAS) AF: 0.00 AC: 0 AN: 79168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077888

Other (OTH) AF: 0.00 AC: 0 AN: 57756

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.097
DANN	Benign	0.70
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.6	N
PhyloP100		-1.9
PrimateAI	Benign	0.38	T
PROVEAN	Benign	2.5	N
REVEL	Benign	0.018
Sift	Benign	1.0	T
Sift4G	Benign	0.60	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.37		Loss of sheet (P = 0.0357)
MVP		0.014
ClinPred		0.69	D
GERP RS		-4.3
Varity_R		0.016
gMVP		0.045
Mutation Taster		=96/4	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: rs777260933; hg19: chr7-100170363;