7-100572714-C-G

Variant names:

• chr7-100572714-C-G
• rs375203122
• NM_001348680.2:c.549G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001348680.2(SAP25):​c.549G>C​(p.Ser183Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 1,535,728 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (2 hom.)
• Consequence: SAP25 NM_001348680.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.31
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-100572714-C-G is Benign according to our data. Variant chr7-100572714-C-G is described in ClinVar as [Benign]. Clinvar id is 732372.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.31 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAP25	NM_001348680.2	c.549G>C	p.Ser183Ser	synonymous_variant	Exon 5 of 6	ENST00000622764.3	NP_001335609.1
SAP25	NM_001168682.3	c.528G>C	p.Ser176Ser	synonymous_variant	Exon 5 of 6		NP_001162153.2
SAP25	NM_001348677.2	c.255G>C	p.Ser85Ser	synonymous_variant	Exon 4 of 5		NP_001335606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SAP25	ENST00000622764.3	c.549G>C	p.Ser183Ser	synonymous_variant	Exon 5 of 6	5	NM_001348680.2	ENSP00000481773.2

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 397 AN: 151796 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00911

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000917

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: 0.0000295

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.000548 AC: 76 AN: 138710 AF XY: 0.000390

Gnomad AFR exome AF: 0.00910

Gnomad AMR exome AF: 0.000245

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: 0.000240

GnomAD4 exome AF: 0.000215 AC: 298 AN: 1383814 Hom.: 2 Cov.: 32 AF XY: 0.000189 AC XY: 129 AN XY: 682904

African (AFR) AF: 0.00779 AC: 246 AN: 31562

American (AMR) AF: 0.000309 AC: 11 AN: 35580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25134

East Asian (EAS) AF: 0.00 AC: 0 AN: 35724

South Asian (SAS) AF: 0.00 AC: 0 AN: 79220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000464 AC: 5 AN: 1078524

Other (OTH) AF: 0.000622 AC: 36 AN: 57866

GnomAD4 genome AF: 0.00261 AC: 397 AN: 151914 Hom.: 2 Cov.: 32 AF XY: 0.00250 AC XY: 186 AN XY: 74262

African (AFR) AF: 0.00908 AC: 376 AN: 41416

American (AMR) AF: 0.000916 AC: 14 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67876

Other (OTH) AF: 0.00237 AC: 5 AN: 2108

Alfa AF: 0.000428 Hom.: 0

Bravo AF: 0.00288

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 27, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.47
DANN	Benign	0.55
PhyloP100		-2.3
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: rs375203122; hg19: chr7-100170337;