rs144929525

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A203T) has been classified as Uncertain significance.

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

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
SUN1	NM_001130965.3 link	c.608C>T	p.Ala203Val	missense_variant	Exon 5 of 19	ENST00000401592.6	NP_001124437.1	O94901-8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN1	ENST00000401592.6 link	c.608C>T	p.Ala203Val	missense_variant	Exon 5 of 19	1	NM_001130965.3	ENSP00000384015.1		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

GnomAD2 exomes

AF:

0.00465

AC:

1158

AN:

248890

AF XY:

0.00480

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 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

African (AFR)

AF:

0.00131

AC:

AN:

33480

American (AMR)

AF:

0.00494

AC:

221

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00696

AC:

182

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00230

AC:

198

AN:

86258

European-Finnish (FIN)

AF:

0.00150

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00792

AC:

8807

AN:

1111908

Other (OTH)

AF:

0.00759

AC:

458

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

694

1388

2082

2776

3470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00488

AC:

743

AN:

152352

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00180

AC:

AN:

41582

American (AMR)

AF:

0.00523

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00248

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00775

AC:

527

AN:

68038

Other (OTH)

AF:

0.00567

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

125

166

208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00609

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SUN1: BP4, BS2 -

SUN1-related disorder

Benign:1

May 02, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

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;.;.

PhyloP100

1.7

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

PromoterAI

0.023

Neutral

(source)

gMVP

0.20

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over