12-118376700-C-G

Variant names:

• chr12-118376700-C-G
• rs754698455
• NM_022491.3:c.9C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_022491.3(SUDS3):​c.9C>G​(p.Ala3Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000588 in 1,361,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A3A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: SUDS3 NM_022491.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 0 publications found

Genes affected

SUDS3 (HGNC:29545): (SDS3 homolog, SIN3A corepressor complex component) SDS3 is a subunit of the histone deacetylase (see HDAC1; MIM 601241)-dependent SIN3A (MIM 607776) corepressor complex (Fleischer et al., 2003 [PubMed 12724404]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-1.9 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022491.3. 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
	SUDS3	NM_022491.3	MANE Select	c.9C>G	p.Ala3Ala	synonymous	Exon 1 of 12	NP_071936.2	Q9H7L9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUDS3	ENST00000543473.2	TSL:1 MANE Select	c.9C>G	p.Ala3Ala	synonymous	Exon 1 of 12	ENSP00000443988.1	Q9H7L9
	SUDS3	ENST00000859517.1		c.9C>G	p.Ala3Ala	synonymous	Exon 1 of 13	ENSP00000529576.1
	SUDS3	ENST00000859515.1		c.9C>G	p.Ala3Ala	synonymous	Exon 1 of 11	ENSP00000529574.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000453 AC: 5 AN: 110344 AF XY: 0.0000649

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: 0.0000236

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000588 AC: 8 AN: 1361092 Hom.: 0 Cov.: 31 AF XY: 0.0000104 AC XY: 7 AN XY: 671866

African (AFR) AF: 0.00 AC: 0 AN: 28272

American (AMR) AF: 0.00 AC: 0 AN: 32452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23990

East Asian (EAS) AF: 0.00 AC: 0 AN: 33408

South Asian (SAS) AF: 0.000105 AC: 8 AN: 76554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4156

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1069662

Other (OTH) AF: 0.00 AC: 0 AN: 56714

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.2
DANN	Benign	0.87
PhyloP100		-1.9
PromoterAI		0.013	Neutral

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: rs754698455; hg19: chr12-118814505;