Genetic Variant SUN1:c.266+144T>C (chr7-839130-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001130965.3(SUN1):c.266+144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 711,780 control chromosomes in the GnomAD database, including 210,662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.78 ( 46045 hom., cov: 34)

Exomes 𝑓: 0.77 ( 164617 hom. )

Consequence

SUN1
NM_001130965.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0850

Publications

7 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=-1.0).

BP6

Variant 7-839130-T-C is Benign according to our data. Variant chr7-839130-T-C is described in ClinVar as [Benign]. Clinvar id is 1253189.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN1	NM_001130965.3 link	c.266+144T>C		intron_variant	Intron 2 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.266+144T>C		intron_variant	Intron 2 of 18	1	NM_001130965.3	ENSP00000384015.1		O94901-8

Frequencies

GnomAD3 genomes

AF:

0.776

AC:

118133

AN:

152146

Hom.:

45990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.754

Gnomad AMI

AF:

0.822

Gnomad AMR

AF:

0.830

Gnomad ASJ

AF:

0.706

Gnomad EAS

AF:

0.807

Gnomad SAS

AF:

0.764

Gnomad FIN

AF:

0.878

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.765

Gnomad OTH

AF:

0.753

GnomAD4 exome

AF:

0.766

AC:

428324

AN:

559516

Hom.:

164617

Cov.:

AF XY:

0.766

AC XY:

214192

AN XY:

279802

show subpopulations

African (AFR)

AF:

0.750

AC:

10157

AN:

13540

American (AMR)

AF:

0.851

AC:

8886

AN:

10444

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

9014

AN:

12556

East Asian (EAS)

AF:

0.795

AC:

20793

AN:

26150

South Asian (SAS)

AF:

0.739

AC:

17600

AN:

23820

European-Finnish (FIN)

AF:

0.866

AC:

21486

AN:

24800

Middle Eastern (MID)

AF:

0.727

AC:

1455

AN:

2002

European-Non Finnish (NFE)

AF:

0.759

AC:

317547

AN:

418272

Other (OTH)

AF:

0.766

AC:

21386

AN:

27932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5103

10207

15310

20414

25517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.777

AC:

118249

AN:

152264

Hom.:

46045

Cov.:

AF XY:

0.781

AC XY:

58158

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.754

AC:

31315

AN:

41528

American (AMR)

AF:

0.830

AC:

12707

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.706

AC:

2450

AN:

3472

East Asian (EAS)

AF:

0.807

AC:

4185

AN:

5186

South Asian (SAS)

AF:

0.763

AC:

3676

AN:

4820

European-Finnish (FIN)

AF:

0.878

AC:

9324

AN:

10614

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.765

AC:

52035

AN:

68016

Other (OTH)

AF:

0.755

AC:

1598

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1414

2829

4243

5658

7072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.768

Hom.:

6198

Bravo

AF:

0.771

Asia WGS

AF:

0.826

AC:

2873

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 15, 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

-1.0

CADD

Benign

2.1

(source)

DANN

Benign

0.43

PhyloP100

-0.085

PromoterAI

-0.0096

Neutral

(source)

Mutation Taster

=100/0

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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chr7-839130-T-C

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