chr3-56296107-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_015576.3(ERC2):c.986C>T(p.Thr329Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,613,922 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: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
ERC2
NM_015576.3 missense
NM_015576.3 missense
Scores
3
3
12
Clinical Significance
Conservation
PhyloP100: 7.92
Genes affected
ERC2 (HGNC:31922): (ELKS/RAB6-interacting/CAST family member 2) This gene encodes a protein that belongs to the Rab3-interacting molecule (RIM)-binding protein family. Members of this protein family form part of the cytomatrix at the active zone (CAZ) complex and function as regulators of neurotransmitter release. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.16775936).
BS2
?
High AC in GnomAd at 28 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERC2 | NM_015576.3 | c.986C>T | p.Thr329Met | missense_variant | 3/18 | ENST00000288221.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERC2 | ENST00000288221.11 | c.986C>T | p.Thr329Met | missense_variant | 3/18 | 1 | NM_015576.3 | P1 | |
ERC2 | ENST00000460849.5 | c.986C>T | p.Thr329Met | missense_variant, NMD_transcript_variant | 3/19 | 1 | |||
ERC2 | ENST00000492584.3 | c.986C>T | p.Thr329Met | missense_variant | 3/18 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152168Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000762 AC: 19AN: 249260Hom.: 0 AF XY: 0.0000887 AC XY: 12AN XY: 135224
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GnomAD4 exome AF: 0.0000315 AC: 46AN: 1461638Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727094
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GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 17AN XY: 74452
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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 | Jan 24, 2024 | The c.986C>T (p.T329M) alteration is located in exon 3 (coding exon 2) of the ERC2 gene. This alteration results from a C to T substitution at nucleotide position 986, causing the threonine (T) at amino acid position 329 to be replaced by a methionine (M). 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
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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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