Genetic Variant NM_022491.3:c.342A>T (chr12-118389928-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022491.3(SUDS3):c.342A>T(p.Glu114Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SUDS3
NM_022491.3 missense, splice_region

Scores

Splicing: ADA: 0.00009091

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0540

Publications

0 publications found

Variant links:

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]

SUDS3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13355836).

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.342A>T	p.Glu114Asp	missense splice_region	Exon 5 of 12	NP_071936.2	Q9H7L9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUDS3	ENST00000543473.2	TSL:1 MANE Select	c.342A>T	p.Glu114Asp	missense splice_region	Exon 5 of 12	ENSP00000443988.1	Q9H7L9
SUDS3	ENST00000859517.1		c.375A>T	p.Glu125Asp	missense splice_region	Exon 6 of 13	ENSP00000529576.1
SUDS3	ENST00000859515.1		c.270A>T	p.Glu90Asp	missense splice_region	Exon 4 of 11	ENSP00000529574.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727130

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111860

Other (OTH)

AF:

0.00

AC:

AN:

60374

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.016

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.15

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.85

M_CAP

Benign

0.0098

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.85

PhyloP100

-0.054

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.7

REVEL

Uncertain

0.33

Sift

Benign

0.33

Sift4G

Benign

0.28

Polyphen

0.0060

Vest4

0.20

MutPred

0.46

Gain of MoRF binding (P = 0.1055)

MVP

0.32

MPC

0.33

ClinPred

0.062

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.33

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000091

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over