Variant chr17-1783036-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052928.3(SMYD4):c.2260G>A(p.Gly754Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000186 in 1,613,662 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SMYD4
NM_052928.3 missense, splice_region

Scores

Splicing: ADA: 0.1651

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

Variant links:

Genes affected

SMYD4 (HGNC:21067): (SET and MYND domain containing 4) Predicted to enable metal ion binding activity and methyltransferase activity. Involved in heart development. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SMYD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMYD4	NM_052928.3 link	c.2260G>A	p.Gly754Arg	missense_variant, splice_region_variant	Exon 10 of 11	ENST00000305513.12	NP_443160.2	Q8IYR2
SMYD4	XM_047435290.1 link	c.2260G>A	p.Gly754Arg	missense_variant	Exon 10 of 10		XP_047291246.1
SMYD4	XM_024450560.2 link	c.2260G>A	p.Gly754Arg	missense_variant, splice_region_variant	Exon 10 of 11		XP_024306328.1
SMYD4	XM_047435291.1 link	c.1948G>A	p.Gly650Arg	missense_variant, splice_region_variant	Exon 9 of 10		XP_047291247.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMYD4	ENST00000305513.12 link	c.2260G>A	p.Gly754Arg	missense_variant, splice_region_variant	Exon 10 of 11	1	NM_052928.3	ENSP00000304360.7		Q8IYR2
SMYD4	ENST00000491788.1 link	c.1672G>A	p.Gly558Arg	missense_variant	Exon 6 of 6	2		ENSP00000460921.1		I3L428

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251026

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461524

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2260G>A (p.G754R) alteration is located in exon 10 (coding exon 9) of the SMYD4 gene. This alteration results from a G to A substitution at nucleotide position 2260, causing the glycine (G) at amino acid position 754 to be replaced by an arginine (R). 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

0.75

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.081

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Uncertain

0.045

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.5

D;.

REVEL

Uncertain

0.47

Sift

Uncertain

0.0020

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.89

MutPred

0.56

Gain of solvent accessibility (P = 0.0674);.;

MVP

0.83

MPC

0.48

ClinPred

0.69

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.61

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.17

dbscSNV1_RF

Benign

0.30

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