Variant rs144929525 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.608C>T(p.Ala203Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00666 in 1,614,090 control chromosomes in the GnomAD database, including 48 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 0.0049 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0068 ( 45 hom. )

Consequence

SUN1
NM_001130965.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.72

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:

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=0.004375726).

BP6

Variant 7-843470-C-T is Benign according to our data. Variant chr7-843470-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 461663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUN1	NM_001130965.3 linkuse as main transcript	c.608C>T	p.Ala203Val	missense_variant	5/19	ENST00000401592.6	NP_001124437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUN1	ENST00000401592.6 linkuse as main transcript	c.608C>T	p.Ala203Val	missense_variant	5/19	1	NM_001130965.3	ENSP00000384015	P3	O94901-8

Frequencies

GnomAD3 genomes

AF:

0.00487

AC:

742

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00523

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00773

Gnomad OTH

AF:

0.00573

GnomAD3 exomes

AF:

0.00465

AC:

1158

AN:

248890

Hom.:

AF XY:

0.00480

AC XY:

649

AN XY:

135262

show subpopulations

Gnomad AFR exome

AF:

0.00182

Gnomad AMR exome

AF:

0.00481

Gnomad ASJ exome

AF:

0.00627

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00255

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00677

Gnomad OTH exome

AF:

0.00512

GnomAD4 exome

AF:

0.00685

AC:

10010

AN:

1461738

Hom.:

Cov.:

AF XY:

0.00669

AC XY:

4865

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00494

Gnomad4 ASJ exome

AF:

0.00696

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00230

Gnomad4 FIN exome

AF:

0.00150

Gnomad4 NFE exome

AF:

0.00792

Gnomad4 OTH exome

AF:

0.00759

GnomAD4 genome

AF:

0.00488

AC:

743

AN:

152352

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00775

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00650

Hom.:

Bravo

AF:

0.00538

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00181

AC:

ESP6500EA

AF:

0.00741

AC:

ExAC

AF:

0.00441

AC:

533

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00747

EpiControl

AF:

0.00771

ClinVar

Significance: Benign/Likely 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2024

SUN1: BP4, BS2 -

SUN1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2019

This variant is classified as likely 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_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.021

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

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.67

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

M_CAP

Benign

0.027

MetaRNN

Benign

0.0044

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.77

.;.;.;N;N;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.23

PROVEAN

Benign

-2.2

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

REVEL

Benign

0.048

Sift

Benign

0.060

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

Sift4G

Benign

0.14

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

Polyphen

0.092

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

Vest4

0.10

MVP

0.12

MPC

0.087

ClinPred

0.0038

GERP RS

1.4

gMVP

0.20

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