Variant rs200378884 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001130965.3(SUN1):c.2199G>A(p.Thr733Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 1,603,006 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 16 hom. )

Consequence

SUN1
NM_001130965.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -4.45

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 7-872520-G-A is Benign according to our data. Variant chr7-872520-G-A is described in ClinVar as [Benign]. Clinvar id is 461650.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.45 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUN1	NM_001130965.3 linkuse as main transcript	c.2199G>A	p.Thr733Thr	synonymous_variant	18/19	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.2199G>A	p.Thr733Thr	synonymous_variant	18/19	1	NM_001130965.3	ENSP00000384015.1		O94901-8

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

409

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00837

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00338

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00299

AC:

683

AN:

228452

Hom.:

AF XY:

0.00309

AC XY:

381

AN XY:

123324

show subpopulations

Gnomad AFR exome

AF:

0.000662

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00881

Gnomad EAS exome

AF:

0.0000591

Gnomad SAS exome

AF:

0.00130

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.00419

Gnomad OTH exome

AF:

0.00493

GnomAD4 exome

AF:

0.00341

AC:

4949

AN:

1450760

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

2441

AN XY:

720320

show subpopulations

Gnomad4 AFR exome

AF:

0.000659

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.00797

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00156

Gnomad4 FIN exome

AF:

0.00227

Gnomad4 NFE exome

AF:

0.00377

Gnomad4 OTH exome

AF:

0.00315

GnomAD4 genome

AF:

0.00269

AC:

409

AN:

152246

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00837

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00338

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00249

Hom.:

Bravo

AF:

0.00259

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

SUN1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.20

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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