dbSNP rs77466627: SUN1:c.78-3T>C (chr7-838795-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The NM_001130965.3(SUN1):c.78-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,538,870 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

SUN1
NM_001130965.3 splice_region, intron

Scores

Splicing: ADA: 0.00001835

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.0490

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-838795-T-C is Benign according to our data. Variant chr7-838795-T-C is described in ClinVar as [Benign]. Clinvar id is 461668.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00154 (234/152364) while in subpopulation EAS AF = 0.0376 (195/5188). AF 95% confidence interval is 0.0333. There are 8 homozygotes in GnomAd4. There are 136 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN1	NM_001130965.3 link	c.78-3T>C		splice_region_variant, intron_variant	Intron 1 of 18	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.78-3T>C		splice_region_variant, intron_variant	Intron 1 of 18	1	NM_001130965.3	ENSP00000384015.1		O94901-8

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

237

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000964

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0381

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00233

AC:

357

AN:

152988

AF XY:

0.00237

show subpopulations

Gnomad AFR exome

AF:

0.000234

Gnomad AMR exome

AF:

0.0000876

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0302

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000496

Gnomad OTH exome

AF:

0.000930

GnomAD4 exome

AF:

0.00114

AC:

1580

AN:

1386506

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

775

AN XY:

681846

show subpopulations

African (AFR)

AF:

0.0000636

AC:

AN:

31438

American (AMR)

AF:

0.000117

AC:

AN:

34202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24632

East Asian (EAS)

AF:

0.0373

AC:

1332

AN:

35740

South Asian (SAS)

AF:

0.000800

AC:

AN:

77546

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49304

Middle Eastern (MID)

AF:

0.000354

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.0000159

AC:

AN:

1070386

Other (OTH)

AF:

0.00279

AC:

161

AN:

57614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

181

272

362

453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00154

AC:

234

AN:

152364

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0000961

AC:

AN:

41604

American (AMR)

AF:

0.00124

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0376

AC:

195

AN:

5188

South Asian (SAS)

AF:

0.00166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68026

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000212

Hom.:

Bravo

AF:

0.00144

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SUN1-related disorder

Benign:1

Jun 13, 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

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.0

(source)

DANN

Benign

0.38

PhyloP100

0.049

PromoterAI

0.0081

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.010

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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rs77466627

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