12-118414397-C-T

Variant names:

• chr12-118414397-C-T
• rs147756379
• NM_022491.3:c.951C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_022491.3(SUDS3):​c.951C>T​(p.Arg317Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00583 in 1,602,612 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (47 hom.)
• Consequence: SUDS3 NM_022491.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.60
• Publications: 2 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 12-118414397-C-T is Benign according to our data. Variant chr12-118414397-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 791587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.61 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 47 AR gene

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.951C>T	p.Arg317Arg	synonymous	Exon 12 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.951C>T	p.Arg317Arg	synonymous	Exon 12 of 12	ENSP00000443988.1	Q9H7L9
	SUDS3	ENST00000859517.1		c.984C>T	p.Arg328Arg	synonymous	Exon 13 of 13	ENSP00000529576.1
	SUDS3	ENST00000859515.1		c.879C>T	p.Arg293Arg	synonymous	Exon 11 of 11	ENSP00000529574.1

Frequencies

GnomAD3 genomes AF: 0.00489 AC: 745 AN: 152218 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00654

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00475 AC: 1085 AN: 228442 AF XY: 0.00460

Gnomad AFR exome AF: 0.00103

Gnomad AMR exome AF: 0.00163

Gnomad ASJ exome AF: 0.00135

Gnomad EAS exome AF: 0.000538

Gnomad FIN exome AF: 0.0131

Gnomad NFE exome AF: 0.00691

Gnomad OTH exome AF: 0.00341

GnomAD4 exome AF: 0.00593 AC: 8602 AN: 1450276 Hom.: 47 Cov.: 30 AF XY: 0.00577 AC XY: 4153 AN XY: 720212

African (AFR) AF: 0.000902 AC: 30 AN: 33244

American (AMR) AF: 0.00134 AC: 58 AN: 43410

Ashkenazi Jewish (ASJ) AF: 0.00108 AC: 28 AN: 25888

East Asian (EAS) AF: 0.000408 AC: 16 AN: 39204

South Asian (SAS) AF: 0.000191 AC: 16 AN: 83812

European-Finnish (FIN) AF: 0.0130 AC: 680 AN: 52332

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5640

European-Non Finnish (NFE) AF: 0.00681 AC: 7532 AN: 1106788

Other (OTH) AF: 0.00402 AC: 241 AN: 59958

GnomAD4 genome AF: 0.00489 AC: 745 AN: 152336 Hom.: 1 Cov.: 32 AF XY: 0.00513 AC XY: 382 AN XY: 74486

African (AFR) AF: 0.00101 AC: 42 AN: 41582

American (AMR) AF: 0.00530 AC: 81 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0137 AC: 145 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00654 AC: 445 AN: 68032

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00544 Hom.: 3

Bravo AF: 0.00373

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.93
DANN	Benign	0.63
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

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: rs147756379; hg19: chr12-118852202; COSMIC: COSV100820046; COSMIC: COSV100820046;