chr15-51806459-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014548.4(TMOD2):c.959A>G(p.Gln320Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,614,134 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 1 hom. )
Consequence
TMOD2
NM_014548.4 missense
NM_014548.4 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
TMOD2 (HGNC:11872): (tropomodulin 2) This gene encodes a neuronal-specific member of the tropomodulin family of actin-regulatory proteins. The encoded protein caps the pointed end of actin filaments preventing both elongation and depolymerization. The capping activity of this protein is dependent on its association with tropomyosin. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2008]
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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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMOD2 | NM_014548.4 | c.959A>G | p.Gln320Arg | missense_variant | 9/10 | ENST00000249700.9 | |
TMOD2 | NM_001142885.2 | c.851A>G | p.Gln284Arg | missense_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMOD2 | ENST00000249700.9 | c.959A>G | p.Gln320Arg | missense_variant | 9/10 | 1 | NM_014548.4 | P1 | |
TMOD2 | ENST00000435126.6 | c.851A>G | p.Gln284Arg | missense_variant | 8/9 | 2 | |||
TMOD2 | ENST00000539962.6 | c.827A>G | p.Gln276Arg | missense_variant | 10/11 | 2 | |||
TMOD2 | ENST00000561407.1 | c.236A>G | p.Gln79Arg | missense_variant, NMD_transcript_variant | 3/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152248Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000135 AC: 34AN: 251378Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135852
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GnomAD4 exome AF: 0.000159 AC: 232AN: 1461886Hom.: 1 Cov.: 31 AF XY: 0.000172 AC XY: 125AN XY: 727242
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74390
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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 12, 2023 | The c.959A>G (p.Q320R) alteration is located in exon 9 (coding exon 8) of the TMOD2 gene. This alteration results from a A to G substitution at nucleotide position 959, causing the glutamine (Q) at amino acid position 320 to be replaced by an arginine (R). 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
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
B;.;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Score
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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