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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAP25	NM_001348680.2	c.612G>T	p.Met204Ile	missense_variant, splice_region_variant	Exon 6 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3	c.591G>T	p.Met197Ile	missense_variant, splice_region_variant	Exon 6 of 6		NP_001162153.2
SAP25	NM_001348677.2	c.318G>T	p.Met106Ile	missense_variant, splice_region_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.612G>T	p.Met204Ile	missense_variant, splice_region_variant	Exon 6 of 6	5	NM_001348680.2	ENSP00000481773.2

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 = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.63	.;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.032	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;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;T;T
Polyphen		0.0	B;.;B
Vest4		0.033
MutPred		0.13		Gain of methylation at K111 (P = 0.1184);.;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;