dbSNP rs200907784: SUN1:p.Val715Ile (chr7-869511-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001130965.3(SUN1):c.2143G>A(p.Val715Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,612,934 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00075 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00080 ( 2 hom. )

Consequence

SUN1
NM_001130965.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 9.69

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:

LOC124901568 (HGNC:):

LOC124901568 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044427216).

BP6

Variant 7-869511-G-A is Benign according to our data. Variant chr7-869511-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 461649.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130965.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUN1	NM_001130965.3	MANE Select	c.2143G>A	p.Val715Ile	missense	Exon 17 of 19	NP_001124437.1	O94901-8
SUN1	NM_001367651.1		c.2557G>A	p.Val853Ile	missense	Exon 20 of 22	NP_001354580.1
SUN1	NM_001367705.1		c.2536G>A	p.Val846Ile	missense	Exon 21 of 23	NP_001354634.1	O94901-9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUN1	ENST00000401592.6	TSL:1 MANE Select	c.2143G>A	p.Val715Ile	missense	Exon 17 of 19	ENSP00000384015.1	O94901-8
SUN1	ENST00000429178.5	TSL:1	c.1918G>A	p.Val640Ile	missense	Exon 15 of 17	ENSP00000409909.1	H0Y742
SUN1	ENST00000475971.5	TSL:1	n.2252G>A		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000837

AC:

208

AN:

248452

AF XY:

0.000928

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.000325

Gnomad NFE exome

AF:

0.00141

Gnomad OTH exome

AF:

0.000831

GnomAD4 exome

AF:

0.000804

AC:

1175

AN:

1460714

Hom.:

Cov.:

AF XY:

0.000884

AC XY:

642

AN XY:

726614

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33456

American (AMR)

AF:

0.000291

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.000882

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.000674

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.000915

AC:

AN:

5462

European-Non Finnish (NFE)

AF:

0.000902

AC:

1002

AN:

1111464

Other (OTH)

AF:

0.000597

AC:

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

125

188

250

313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000749

AC:

114

AN:

152220

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41516

American (AMR)

AF:

0.000131

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.000830

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00144

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00124

Hom.:

Bravo

AF:

0.000608

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000710

AC:

ExAC

AF:

0.00105

AC:

127

EpiCase

AF:

0.000873

EpiControl

AF:

0.000535

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Emery-Dreifuss muscular dystrophy (1)

not provided (1)

not specified (1)

SUN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.054

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

M_CAP

Benign

0.020

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.56

PhyloP100

9.7

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.88

REVEL

Benign

0.24

Sift

Benign

0.31

Sift4G

Benign

0.38

Polyphen

1.0

Vest4

0.69

MVP

0.42

MPC

1.5

ClinPred

0.047

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.73

Mutation Taster

=87/13

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over