2-73221862-C-A
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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.574C>A(p.Gln192Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SMYD5
NM_006062.3 missense
NM_006062.3 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 5.47
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=0.29464096).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMYD5 | NM_006062.3 | c.574C>A | p.Gln192Lys | missense_variant | 6/13 | ENST00000389501.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMYD5 | ENST00000389501.9 | c.574C>A | p.Gln192Lys | missense_variant | 6/13 | 1 | NM_006062.3 | P1 | |
SMYD5 | ENST00000474652.1 | n.693C>A | non_coding_transcript_exon_variant | 6/6 | 5 | ||||
SMYD5 | ENST00000477038.1 | n.96C>A | non_coding_transcript_exon_variant | 2/4 | 5 | ||||
SMYD5 | ENST00000258100.8 | c.*342C>A | 3_prime_UTR_variant, NMD_transcript_variant | 6/8 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251484Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461724Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 727182
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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 | May 31, 2023 | The c.574C>A (p.Q192K) alteration is located in exon 6 (coding exon 6) of the SMYD5 gene. This alteration results from a C to A substitution at nucleotide position 574, causing the glutamine (Q) at amino acid position 192 to be replaced by a lysine (K). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of ubiquitination at Q192 (P = 0.0109);
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