14-64076025-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182914.3(SYNE2):​c.10947G>C​(p.Met3649Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)

Consequence

SYNE2
NM_182914.3 missense

Scores

1
10
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.76
Variant links:
Genes affected
SYNE2 (HGNC:17084): (spectrin repeat containing nuclear envelope protein 2) The protein encoded by this gene is a nuclear outer membrane protein that binds cytoplasmic F-actin. This binding tethers the nucleus to the cytoskeleton and aids in the maintenance of the structural integrity of the nucleus. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

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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=0.3009968).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNE2NM_182914.3 linkc.10947G>C p.Met3649Ile missense_variant Exon 54 of 116 ENST00000555002.6 NP_878918.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNE2ENST00000555002.6 linkc.10947G>C p.Met3649Ile missense_variant Exon 54 of 116 1 NM_182914.3 ENSP00000450831.2 Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
31
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Uncertain
0.017
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.028
.;T;T;T;T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.86
D;D;D;D;D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.30
T;T;T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Uncertain
2.7
M;.;M;.;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-1.8
N;.;N;N;N
REVEL
Benign
0.085
Sift
Uncertain
0.013
D;.;D;D;D
Sift4G
Uncertain
0.0050
D;D;D;D;D
Polyphen
0.95
P;.;P;.;.
Vest4
0.54
MutPred
0.36
Gain of catalytic residue at M3649 (P = 0.0579);.;Gain of catalytic residue at M3649 (P = 0.0579);.;.;
MVP
0.50
MPC
0.21
ClinPred
0.80
D
GERP RS
5.8
Varity_R
0.33
gMVP
0.40

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: rs772140514; hg19: chr14-64542743; API