Variant rs199999269 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001130965.3(SUN1):c.235A>G(p.Ser79Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,605,106 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 8 hom. )

Consequence

SUN1
NM_001130965.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.894

Variant links:

Genes affected

SUN1 (HGNC:18587): (Sad1 and UNC84 domain containing 1) This gene is a member of the unc-84 homolog family and encodes a nuclear envelope protein with an Unc84 (SUN) domain. The protein is involved in nuclear anchorage and migration. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jan 2019]

SUN1 links:

SUN1 (HGNC:):

SUN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058339536).

BP6

Variant 7-838955-A-G is Benign according to our data. Variant chr7-838955-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 461656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUN1	NM_001130965.3 linkuse as main transcript	c.235A>G	p.Ser79Gly	missense_variant	2/19	ENST00000401592.6	NP_001124437.1	O94901-8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUN1	ENST00000401592.6 linkuse as main transcript	c.235A>G	p.Ser79Gly	missense_variant	2/19	1	NM_001130965.3	ENSP00000384015.1		O94901-8

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00106

AC:

247

AN:

233548

Hom.:

AF XY:

0.00104

AC XY:

132

AN XY:

126834

show subpopulations

Gnomad AFR exome

AF:

0.000284

Gnomad AMR exome

AF:

0.000278

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00207

Gnomad FIN exome

AF:

0.00223

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00177

GnomAD4 exome

AF:

0.00127

AC:

1846

AN:

1452778

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

891

AN XY:

721770

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00201

Gnomad4 FIN exome

AF:

0.00251

Gnomad4 NFE exome

AF:

0.00133

Gnomad4 OTH exome

AF:

0.000866

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152328

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000706

Hom.:

Bravo

AF:

0.000623

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000494

AC:

ESP6500EA

AF:

0.00190

AC:

ExAC

AF:

0.00108

AC:

130

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 27, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

SUN1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.2

DANN

Benign

0.39

DEOGEN2

Benign

0.025

.;.;.;.;T;T;T;.;T;T;.;.;.;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.72

T;.;T;T;.;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.0058

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;.;L;.;.;.;.;.;.;.;L;L;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.32

T;T;D;T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.27

T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.0040

.;B;.;.;.;.;.;.;.;.;.;.;B;.

Vest4

0.16

MVP

0.23

MPC

0.080

ClinPred

0.020

GERP RS

4.4

gMVP

0.15

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.

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