2-73221881-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006062.3(SMYD5):c.593C>T(p.Ala198Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,613,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
SMYD5
NM_006062.3 missense
NM_006062.3 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 5.58
Genes affected
SMYD5 (HGNC:16258): (SMYD family member 5) Predicted to enable histone methyltransferase activity (H4-K20 specific). Involved in negative regulation of transposition and regulation of stem cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35144728).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMYD5 | NM_006062.3 | c.593C>T | p.Ala198Val | missense_variant | 6/13 | ENST00000389501.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMYD5 | ENST00000389501.9 | c.593C>T | p.Ala198Val | missense_variant | 6/13 | 1 | NM_006062.3 | P1 | |
SMYD5 | ENST00000474652.1 | n.712C>T | non_coding_transcript_exon_variant | 6/6 | 5 | ||||
SMYD5 | ENST00000477038.1 | n.115C>T | non_coding_transcript_exon_variant | 2/4 | 5 | ||||
SMYD5 | ENST00000258100.8 | c.*361C>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/8 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251482Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135914
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461524Hom.: 0 Cov.: 29 AF XY: 0.00000825 AC XY: 6AN XY: 727110
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74316
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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 | Jul 09, 2021 | The c.593C>T (p.A198V) alteration is located in exon 6 (coding exon 6) of the SMYD5 gene. This alteration results from a C to T substitution at nucleotide position 593, causing the alanine (A) at amino acid position 198 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of helix (P = 0.0425);
MVP
MPC
ClinPred
T
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