dbSNP rs199999269: SUN1:p.Ser79Gly (chr7-838955-A-G) – ACMG Classification: Benign (-16 pts)

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.235A>G(p.Ser79Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,605,106 control chromosomes in the GnomAD database, including 8 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 (★★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 8 hom. )

Consequence

SUN1
NM_001130965.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.894

Publications

2 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=0.0058339536).

BP6

Variant 7-838955-A-G is Benign according to our data. Variant chr7-838955-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 461656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN1	NM_001130965.3 link	c.235A>G	p.Ser79Gly	missense_variant	Exon 2 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.235A>G	p.Ser79Gly	missense_variant	Exon 2 of 19	1	NM_001130965.3	ENSP00000384015.1

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00106

AC:

247

AN:

233548

AF XY:

0.00104

show subpopulations

Gnomad AFR exome

AF:

0.000284

Gnomad AMR exome

AF:

0.000278

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00223

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00177

GnomAD4 exome

AF:

0.00127

AC:

1846

AN:

1452778

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

891

AN XY:

721770

show subpopulations

African (AFR)

AF:

0.0000600

AC:

AN:

33314

American (AMR)

AF:

0.000231

AC:

AN:

43314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25784

East Asian (EAS)

AF:

0.00

AC:

AN:

39494

South Asian (SAS)

AF:

0.00201

AC:

169

AN:

84150

European-Finnish (FIN)

AF:

0.00251

AC:

131

AN:

52216

Middle Eastern (MID)

AF:

0.000522

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00133

AC:

1479

AN:

1108728

Other (OTH)

AF:

0.000866

AC:

AN:

60036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

107

214

320

427

534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

124

186

248

310

<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:

0.000663

AC:

101

AN:

152328

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41580

American (AMR)

AF:

0.000327

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000838

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000633

Hom.:

Bravo

AF:

0.000623

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000494

AC:

ESP6500EA

AF:

0.00190

AC:

ExAC

AF:

0.00108

AC:

130

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy

Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SUN1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.2

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.025

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

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.72

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

M_CAP

Benign

0.0072

MetaRNN

Benign

0.0058

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;.;L;.;.;.;.;.;.;.;L;L;.;.

PhyloP100

0.89

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

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

REVEL

Benign

0.11

Sift

Benign

0.32

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

Sift4G

Benign

0.27

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

Polyphen

0.0040

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

Vest4

0.16

MVP

0.23

MPC

0.080

ClinPred

0.020

GERP RS

4.4

PromoterAI

0.0028

Neutral

(source)

gMVP

0.15

Mutation Taster

=98/2

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