rs78842948

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001130965.3(SUN1):c.278A>C(p.Gln93Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0028 in 1,614,168 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 57 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 47 hom. )

Consequence

SUN1
NM_001130965.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.45

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038112998).

BP6

Variant 7-841957-A-C is Benign according to our data. Variant chr7-841957-A-C is described in ClinVar as Benign. ClinVar VariationId is 461658.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.014 (2133/152340) while in subpopulation AFR AF = 0.0482 (2002/41574). AF 95% confidence interval is 0.0464. There are 57 homozygotes in GnomAd4. There are 1029 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 57 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN1	NM_001130965.3 link	c.278A>C	p.Gln93Pro	missense_variant	Exon 3 of 19	ENST00000401592.6	NP_001124437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN1	ENST00000401592.6 link	c.278A>C	p.Gln93Pro	missense_variant	Exon 3 of 19	1	NM_001130965.3	ENSP00000384015.1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2130

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.00350

AC:

874

AN:

249398

AF XY:

0.00253

show subpopulations

Gnomad AFR exome

AF:

0.0490

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00163

AC:

2387

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1026

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.0511

AC:

1712

AN:

33478

American (AMR)

AF:

0.00268

AC:

120

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000151

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000269

AC:

299

AN:

1112002

Other (OTH)

AF:

0.00369

AC:

223

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

125

249

374

498

623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<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:

0.0140

AC:

2133

AN:

152340

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1029

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0482

AC:

2002

AN:

41574

American (AMR)

AF:

0.00529

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68034

Other (OTH)

AF:

0.0137

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

108

216

325

433

541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00546

Hom.:

Bravo

AF:

0.0164

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0371

AC:

145

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.00421

AC:

509

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SUN1-related disorder

Benign:1

Apr 02, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

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

Eigen

Benign

0.18

Eigen_PC

Benign

0.081

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

D;.;T;T;T;D;D;D;D;D;D;D

MetaRNN

Benign

0.0038

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

.;.;M;.;.;.;.;.;M;M;.;.

PhyloP100

6.4

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-5.3

D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0070

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

Sift4G

Uncertain

0.0070

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

Polyphen

1.0

.;D;.;.;.;.;.;.;.;.;D;.

Vest4

0.57

MVP

0.33

MPC

0.51

ClinPred

0.060

GERP RS

4.5

gMVP

0.18

Mutation Taster

=97/3

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