rs1207093309

Variant names:

• chr7-100572569-C-A
• rs1207093309
• NM_001348680.2:c.612G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-100572569-C-A
• chr7-100572569-C-T

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.612G>T​(p.Met204Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,304,418 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. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: SAP25 NM_001348680.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• 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=0.03160134).

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.612G>T	p.Met204Ile	missense splice_region	Exon 6 of 6	NP_001335609.1	A0A087WYF9
	SAP25	NM_001168682.3		c.591G>T	p.Met197Ile	missense splice_region	Exon 6 of 6	NP_001162153.2
	SAP25	NM_001348677.2		c.318G>T	p.Met106Ile	missense splice_region	Exon 5 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.612G>T	p.Met204Ile	missense splice_region	Exon 6 of 6	ENSP00000481773.2	A0A087WYF9
	SAP25	ENST00000538735.5	TSL:3	c.318G>T	p.Met106Ile	missense splice_region	Exon 6 of 6	ENSP00000442339.1	Q8TEE9
	SAP25	ENST00000614631.4	TSL:2	c.318G>T	p.Met106Ile	missense splice_region	Exon 5 of 5	ENSP00000481351.1	Q8TEE9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.67e-7 AC: 1 AN: 1304418 Hom.: 0 Cov.: 32 AF XY: 0.00000157 AC XY: 1 AN XY: 636348

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

African (AFR) AF: 0.0000352 AC: 1 AN: 28386

American (AMR) AF: 0.00 AC: 0 AN: 22508

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20034

East Asian (EAS) AF: 0.00 AC: 0 AN: 33944

South Asian (SAS) AF: 0.00 AC: 0 AN: 68040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1040264

Other (OTH) AF: 0.00 AC: 0 AN: 54218

⚠️ 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	0.25
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.8
DANN	Benign	0.93
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.18
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.032
Sift	Benign	0.090	T
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.033
MutPred		0.13		Gain of methylation at K111 (P = 0.1184)
MVP		0.030
ClinPred		0.066	T
GERP RS		-1.4
Varity_R		0.079
gMVP		0.070
Mutation Taster		=97/3	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: rs1207093309; hg19: chr7-100170192;