15-34084386-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_020154.3(EMC7):c.677C>T(p.Ser226Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,758 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
EMC7
NM_020154.3 missense
NM_020154.3 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 9.12
Genes affected
EMC7 (HGNC:24301): (ER membrane protein complex subunit 7) Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Is integral component of endoplasmic reticulum membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.10747501).
BS2
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EMC7 | NM_020154.3 | c.677C>T | p.Ser226Phe | missense_variant | 5/5 | ENST00000256545.9 | NP_064539.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EMC7 | ENST00000256545.9 | c.677C>T | p.Ser226Phe | missense_variant | 5/5 | 1 | NM_020154.3 | ENSP00000256545 | P1 | |
EMC7 | ENST00000527822.5 | c.527C>T | p.Ser176Phe | missense_variant | 4/4 | 2 | ENSP00000434292 | |||
EMC7 | ENST00000528949.1 | c.458C>T | p.Ser153Phe | missense_variant | 5/5 | 3 | ENSP00000434496 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251198Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135768
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461464Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 727042
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74470
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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 | May 20, 2024 | The c.677C>T (p.S226F) alteration is located in exon 5 (coding exon 5) of the EMC7 gene. This alteration results from a C to T substitution at nucleotide position 677, causing the serine (S) at amino acid position 226 to be replaced by a phenylalanine (F). 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
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
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