Variant 14-95436965-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152592.6(SYNE3):c.2393A>G(p.Glu798Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,611,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SYNE3
NM_152592.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.538

Variant links:

Genes affected

SYNE3 (HGNC:19861): (spectrin repeat containing nuclear envelope family member 3) Enables actin filament binding activity and cytoskeleton-nuclear membrane anchor activity. Involved in cytoskeleton organization; establishment of protein localization to membrane; and regulation of cell shape. Located in nuclear membrane. Part of meiotic nuclear membrane microtubule tethering complex. Biomarker of Huntington's disease. [provided by Alliance of Genome Resources, Apr 2022]

SYNE3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08400431).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE3	NM_152592.6 linkuse as main transcript	c.2393A>G	p.Glu798Gly	missense_variant	15/18	ENST00000682763.1	NP_689805.3
SYNE3	NM_001363692.2 linkuse as main transcript	c.2378A>G	p.Glu793Gly	missense_variant, splice_region_variant	15/18		NP_001350621.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SYNE3	ENST00000682763.1 linkuse as main transcript	c.2393A>G	p.Glu798Gly	missense_variant	15/18		NM_152592.6	ENSP00000507501.1	Q6ZMZ3-1
SYNE3	ENST00000334258.9 linkuse as main transcript	c.2393A>G	p.Glu798Gly	missense_variant	14/17	1		ENSP00000334308.4	Q6ZMZ3-1
SYNE3	ENST00000554873.5 linkuse as main transcript	c.1664A>G	p.Glu555Gly	missense_variant	10/13	5		ENSP00000452154.1	G3V533
SYNE3	ENST00000557275.5 linkuse as main transcript	c.2378A>G	p.Glu793Gly	missense_variant, splice_region_variant	14/17	2		ENSP00000450562.1	Q6ZMZ3-2

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149154

Hom.:

Cov.:

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:

0.0000299

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

246300

Hom.:

AF XY:

0.00000752

AC XY:

AN XY:

132924

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149154

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72668

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:

0.0000299

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000832

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000601

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

Sep 26, 2023

The c.2393A>G (p.E798G) alteration is located in exon 14 (coding exon 14) of the SYNE3 gene. This alteration results from a A to G substitution at nucleotide position 2393, causing the glutamic acid (E) at amino acid position 798 to be replaced by a glycine (G). 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

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.011

.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.26

T;T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

.;L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.5

N;D;N

REVEL

Benign

0.035

Sift

Benign

0.25

T;T;T

Sift4G

Benign

0.27

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.20

MutPred

0.34

.;Gain of catalytic residue at E800 (P = 0.0155);.;

MVP

0.19

MPC

0.13

ClinPred

0.028

GERP RS

-2.3

Varity_R

0.058

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over