7-100572880-T-C

Variant names:

• chr7-100572880-T-C
• rs994051311
• NM_001348680.2:c.491A>G

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.491A>G​(p.Gln164Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000478 in 1,463,330 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: SAP25 NM_001348680.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.289
• 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=0.06968215).

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.491A>G	p.Gln164Arg	missense	Exon 4 of 6	NP_001335609.1	A0A087WYF9
	SAP25	NM_001168682.3		c.470A>G	p.Gln157Arg	missense	Exon 4 of 6	NP_001162153.2
	SAP25	NM_001348677.2		c.197A>G	p.Gln66Arg	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.491A>G	p.Gln164Arg	missense	Exon 4 of 6	ENSP00000481773.2	A0A087WYF9
	SAP25	ENST00000538735.5	TSL:3	c.197A>G	p.Gln66Arg	missense	Exon 4 of 6	ENSP00000442339.1	Q8TEE9
	SAP25	ENST00000614631.4	TSL:2	c.197A>G	p.Gln66Arg	missense	Exon 3 of 5	ENSP00000481351.1	Q8TEE9

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152016 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000381 AC: 5 AN: 1311314 Hom.: 0 Cov.: 32 AF XY: 0.00000469 AC XY: 3 AN XY: 640306

African (AFR) AF: 0.00 AC: 0 AN: 28760

American (AMR) AF: 0.00 AC: 0 AN: 23016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20070

East Asian (EAS) AF: 0.00 AC: 0 AN: 35118

South Asian (SAS) AF: 0.00 AC: 0 AN: 68326

European-Finnish (FIN) AF: 0.0000316 AC: 1 AN: 31676

Middle Eastern (MID) AF: 0.000377 AC: 2 AN: 5308

European-Non Finnish (NFE) AF: 0.00000191 AC: 2 AN: 1044456

Other (OTH) AF: 0.00 AC: 0 AN: 54584

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152016 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74252

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

African (AFR) AF: 0.00 AC: 0 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67946

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.095
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.29
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.034
Sift	Benign	0.050	D
Sift4G	Benign	0.20	T
Polyphen		0.22	B
Vest4		0.056
MutPred		0.17		Loss of solvent accessibility (P = 0.1279)
MVP		0.014
ClinPred		0.092	T
GERP RS		1.8
Varity_R		0.059
gMVP		0.038
Mutation Taster		=99/1	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: rs994051311; hg19: chr7-100170503;