Variant rs61744747 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001130965.3(SUN1):c.2043G>A(p.Arg681=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,613,780 control chromosomes in the GnomAD database, including 731 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 58 hom., cov: 32)

Exomes 𝑓: 0.014 ( 673 hom. )

Consequence

SUN1
NM_001130965.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0520

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:

LOC124901568 (HGNC:):

LOC124901568 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 7-869411-G-A is Benign according to our data. Variant chr7-869411-G-A is described in ClinVar as [Benign]. Clinvar id is 461646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.052 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUN1	NM_001130965.3 linkuse as main transcript	c.2043G>A	p.Arg681=	synonymous_variant	17/19	ENST00000401592.6
LOC124901568	XR_007060177.1 linkuse as main transcript	n.282-1718C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUN1	ENST00000401592.6 linkuse as main transcript	c.2043G>A	p.Arg681=	synonymous_variant	17/19	1	NM_001130965.3	P3	O94901-8

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2045

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.0270

Gnomad FIN

AF:

0.0312

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00910

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.0223

AC:

5565

AN:

249268

Hom.:

249

AF XY:

0.0226

AC XY:

3056

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.00307

Gnomad ASJ exome

AF:

0.0176

Gnomad EAS exome

AF:

0.149

Gnomad SAS exome

AF:

0.0280

Gnomad FIN exome

AF:

0.0290

Gnomad NFE exome

AF:

0.00889

Gnomad OTH exome

AF:

0.0159

GnomAD4 exome

AF:

0.0135

AC:

19754

AN:

1461656

Hom.:

673

Cov.:

AF XY:

0.0142

AC XY:

10350

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00320

Gnomad4 ASJ exome

AF:

0.0178

Gnomad4 EAS exome

AF:

0.152

Gnomad4 SAS exome

AF:

0.0277

Gnomad4 FIN exome

AF:

0.0275

Gnomad4 NFE exome

AF:

0.00719

Gnomad4 OTH exome

AF:

0.0171

GnomAD4 genome

AF:

0.0134

AC:

2043

AN:

152124

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1157

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.140

Gnomad4 SAS

AF:

0.0262

Gnomad4 FIN

AF:

0.0312

Gnomad4 NFE

AF:

0.00910

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00973

Hom.:

Bravo

AF:

0.0119

Asia WGS

AF:

0.0640

AC:

220

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

SUN1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 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

-0.50

CADD

Benign

7.5

DANN

Benign

0.48

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