12-118411153-A-T

Variant names:

• chr12-118411153-A-T
• rs370752292
• NM_022491.3:c.884A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_022491.3(SUDS3):​c.884A>T​(p.Asn295Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000695 in 1,437,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N295S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SUDS3 NM_022491.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.95
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

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.884A>T	p.Asn295Ile	missense	Exon 11 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.884A>T	p.Asn295Ile	missense	Exon 11 of 12	ENSP00000443988.1	Q9H7L9
	SUDS3	ENST00000859517.1		c.917A>T	p.Asn306Ile	missense	Exon 12 of 13	ENSP00000529576.1
	SUDS3	ENST00000859515.1		c.812A>T	p.Asn271Ile	missense	Exon 10 of 11	ENSP00000529574.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1437836 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 712668

African (AFR) AF: 0.00 AC: 0 AN: 33002

American (AMR) AF: 0.00 AC: 0 AN: 41040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25626

East Asian (EAS) AF: 0.00 AC: 0 AN: 38822

South Asian (SAS) AF: 0.00 AC: 0 AN: 82138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1099828

Other (OTH) AF: 0.00 AC: 0 AN: 59634

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.0
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.28
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.024	D
Polyphen		0.99	D
Vest4		0.80
MutPred		0.46		Loss of loop (P = 0.0112)
MVP		0.63
MPC		2.0
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.76
gMVP		0.60
Mutation Taster		=51/49	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: rs370752292; hg19: chr12-118848958;