dbSNP rs76073621: SUN1:p.Thr38Thr (chr7-838834-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001130965.3(SUN1):c.114G>A(p.Thr38Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00614 in 1,566,222 control chromosomes in the GnomAD database, including 543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 52 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 491 hom. )

Consequence

SUN1
NM_001130965.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.800

Publications

4 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 7-838834-G-A is Benign according to our data. Variant chr7-838834-G-A is described in ClinVar as Benign. ClinVar VariationId is 461639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.8 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN1	NM_001130965.3 link	c.114G>A	p.Thr38Thr	synonymous_variant	Exon 2 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.114G>A	p.Thr38Thr	synonymous_variant	Exon 2 of 19	1	NM_001130965.3	ENSP00000384015.1		O94901-8

Frequencies

GnomAD3 genomes

AF:

0.00759

AC:

1155

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0242

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00163

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.0147

AC:

2640

AN:

180074

AF XY:

0.0141

show subpopulations

Gnomad AFR exome

AF:

0.000275

Gnomad AMR exome

AF:

0.000473

Gnomad ASJ exome

AF:

0.00333

Gnomad EAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.0206

Gnomad NFE exome

AF:

0.00142

Gnomad OTH exome

AF:

0.00670

GnomAD4 exome

AF:

0.00598

AC:

8456

AN:

1413980

Hom.:

491

Cov.:

AF XY:

0.00604

AC XY:

4222

AN XY:

698708

show subpopulations

African (AFR)

AF:

0.000153

AC:

AN:

32786

American (AMR)

AF:

0.000409

AC:

AN:

36666

Ashkenazi Jewish (ASJ)

AF:

0.00294

AC:

AN:

25196

East Asian (EAS)

AF:

0.152

AC:

5752

AN:

37828

South Asian (SAS)

AF:

0.00376

AC:

301

AN:

79998

European-Finnish (FIN)

AF:

0.0202

AC:

1024

AN:

50596

Middle Eastern (MID)

AF:

0.00280

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.000723

AC:

785

AN:

1086488

Other (OTH)

AF:

0.00824

AC:

484

AN:

58714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

406

813

1219

1626

2032

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

0.00760

AC:

1157

AN:

152242

Hom.:

Cov.:

AF XY:

0.00973

AC XY:

724

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41550

American (AMR)

AF:

0.000850

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3468

East Asian (EAS)

AF:

0.140

AC:

721

AN:

5166

South Asian (SAS)

AF:

0.00477

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0242

AC:

257

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00163

AC:

111

AN:

68010

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

113

170

226

283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00225

Hom.:

Bravo

AF:

0.00678

Asia WGS

AF:

0.0580

AC:

201

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

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SUN1-related disorder

Benign:1

Feb 28, 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). -

not provided

Benign:1

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

3.6

(source)

DANN

Benign

0.88

PhyloP100

-0.80

PromoterAI

0.0093

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=299/1

polymorphism (auto)

(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