1-246335405-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001167740.2(SMYD3):āc.298G>Cā(p.Asp100His) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 33)
Exomes š: 0.000027 ( 0 hom. )
Consequence
SMYD3
NM_001167740.2 missense
NM_001167740.2 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 3.75
Genes affected
SMYD3 (HGNC:15513): (SET and MYND domain containing 3) This gene encodes a histone methyltransferase which functions in RNA polymerase II complexes by an interaction with a specific RNA helicase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152142Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251448Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135896
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461828Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727216
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74328
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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 02, 2024 | The c.298G>C (p.D100H) alteration is located in exon 3 (coding exon 3) of the SMYD3 gene. This alteration results from a G to C substitution at nucleotide position 298, causing the aspartic acid (D) at amino acid position 100 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;T;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;.;D;D;D
REVEL
Benign
Sift
Uncertain
.;.;D;D;D
Sift4G
Uncertain
D;D;.;D;D
Polyphen
1.0
.;D;.;.;.
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at