15-34084386-G-A

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

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.12
Variant links:
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]

Genome browser will be placed here

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
EMC7NM_020154.3 linkuse as main transcriptc.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
EMC7ENST00000256545.9 linkuse as main transcriptc.677C>T p.Ser226Phe missense_variant 5/51 NM_020154.3 ENSP00000256545 P1
EMC7ENST00000527822.5 linkuse as main transcriptc.527C>T p.Ser176Phe missense_variant 4/42 ENSP00000434292
EMC7ENST00000528949.1 linkuse as main transcriptc.458C>T p.Ser153Phe missense_variant 5/53 ENSP00000434496

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152176
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251198
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135768
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461464
Hom.:
0
Cov.:
30
AF XY:
0.0000165
AC XY:
12
AN XY:
727042
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152294
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000494
AC:
6

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 submitterclinical testingAmbry GeneticsMay 20, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.35
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.089
T;T
Eigen
Benign
-0.079
Eigen_PC
Benign
0.13
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.11
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-2.4
N;D
REVEL
Benign
0.20
Sift
Uncertain
0.028
D;D
Sift4G
Uncertain
0.049
D;D
Polyphen
0.0010
B;.
Vest4
0.31
MVP
0.10
MPC
0.73
ClinPred
0.22
T
GERP RS
4.3
Varity_R
0.12
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs183304201; hg19: chr15-34376587; API