Variant 1-214281396-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020197.3(SMYD2):c.142C>T(p.Arg48Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,463,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

SMYD2
NM_020197.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Variant links:

Genes affected

SMYD2 (HGNC:20982): (SET and MYND domain containing 2) SET domain-containing proteins, such as SMYD2, catalyze lysine methylation (Brown et al., 2006 [PubMed 16805913]).[supplied by OMIM, Nov 2008]

SMYD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.791

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SMYD2	NM_020197.3 linkuse as main transcript	c.142C>T	p.Arg48Trp	missense_variant	1/12	ENST00000366957.10
SMYD2	XM_047425702.1 linkuse as main transcript	c.142C>T	p.Arg48Trp	missense_variant	1/9
SMYD2	XM_047425700.1 linkuse as main transcript	c.-47C>T		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMYD2	ENST00000366957.10 linkuse as main transcript	c.142C>T	p.Arg48Trp	missense_variant	1/12	1	NM_020197.3	P1	Q9NRG4-1
SMYD2	ENST00000460580.5 linkuse as main transcript	n.175C>T		non_coding_transcript_exon_variant	1/11	1
SMYD2	ENST00000471645.5 linkuse as main transcript	n.272C>T		non_coding_transcript_exon_variant	1/10	1
SMYD2	ENST00000491455.5 linkuse as main transcript	n.295C>T		non_coding_transcript_exon_variant	1/11	2

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151364

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000884

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000711

AC:

AN:

168714

Hom.:

AF XY:

0.0000728

AC XY:

AN XY:

96204

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000496

Gnomad NFE exome

AF:

0.000139

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000154

AC:

202

AN:

1311538

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

100

AN XY:

650972

show subpopulations

Gnomad4 AFR exome

AF:

0.0000370

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000209

Gnomad4 NFE exome

AF:

0.000189

Gnomad4 OTH exome

AF:

0.0000765

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151472

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74064

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000885

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000350

AC:

ExAC

AF:

0.0000751

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.142C>T (p.R48W) alteration is located in exon 1 (coding exon 1) of the SMYD2 gene. This alteration results from a C to T substitution at nucleotide position 142, causing the arginine (R) at amino acid position 48 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

0.070

Eigen_PC

Benign

-0.050

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.99

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.7

REVEL

Pathogenic

0.65

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.62

MVP

0.93

MPC

0.73

ClinPred

0.91

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.82

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over