rs770179582

Variant summary

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

The NM_052928.3(SMYD4):​c.2330C>T​(p.Pro777Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SMYD4
NM_052928.3 missense

Scores

4
5
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.93
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]

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
SMYD4NM_052928.3 linkc.2330C>T p.Pro777Leu missense_variant Exon 11 of 11 ENST00000305513.12 NP_443160.2 Q8IYR2
SMYD4XM_024450560.2 linkc.2330C>T p.Pro777Leu missense_variant Exon 11 of 11 XP_024306328.1
SMYD4XM_047435291.1 linkc.2018C>T p.Pro673Leu missense_variant Exon 10 of 10 XP_047291247.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SMYD4ENST00000305513.12 linkc.2330C>T p.Pro777Leu missense_variant Exon 11 of 11 1 NM_052928.3 ENSP00000304360.7 Q8IYR2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251458
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135910
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:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461846
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000205
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.097
BayesDel_addAF
Benign
-0.059
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.049
T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.053
D
MetaRNN
Uncertain
0.60
D
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.38
T
PROVEAN
Pathogenic
-5.9
D
REVEL
Benign
0.27
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.46
MutPred
0.57
Loss of disorder (P = 0.0707);
MVP
0.67
MPC
0.42
ClinPred
0.99
D
GERP RS
4.0
Varity_R
0.63
gMVP
0.49

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.

Other links and lift over

dbSNP: rs770179582; hg19: chr17-1684665; API