dbSNP rs114701323: SUN1:p.Ala587Val (chr7-860363-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001130965.3(SUN1):c.1760C>T(p.Ala587Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000335 in 1,613,742 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

SUN1
NM_001130965.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.838

Publications

6 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028201938).

BP6

Variant 7-860363-C-T is Benign according to our data. Variant chr7-860363-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 530830.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 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.1760C>T	p.Ala587Val	missense	Exon 14 of 19	NP_001124437.1	O94901-8
SUN1	NM_001367651.1		c.2174C>T	p.Ala725Val	missense	Exon 17 of 22	NP_001354580.1
SUN1	NM_001367705.1		c.2153C>T	p.Ala718Val	missense	Exon 18 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.1760C>T	p.Ala587Val	missense	Exon 14 of 19	ENSP00000384015.1	O94901-8
SUN1	ENST00000429178.5	TSL:1	c.1535C>T	p.Ala512Val	missense	Exon 12 of 17	ENSP00000409909.1	H0Y742
SUN1	ENST00000475971.5	TSL:1	n.1869C>T		non_coding_transcript_exon	Exon 5 of 10

Frequencies

GnomAD3 genomes

AF:

0.00188

AC:

286

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000493

AC:

122

AN:

247582

AF XY:

0.000394

show subpopulations

Gnomad AFR exome

AF:

0.00713

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000897

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000174

AC:

254

AN:

1461436

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

113

AN XY:

726956

show subpopulations

African (AFR)

AF:

0.00609

AC:

204

AN:

33476

American (AMR)

AF:

0.000358

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111734

Other (OTH)

AF:

0.000397

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00188

AC:

287

AN:

152306

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00652

AC:

271

AN:

41568

American (AMR)

AF:

0.000719

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68036

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.000880

Hom.:

Bravo

AF:

0.00227

ESP6500AA

AF:

0.00597

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000562

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Emery-Dreifuss muscular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.5

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.0034

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.73

M_CAP

Benign

0.015

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.0

PhyloP100

0.84

PrimateAI

Benign

0.24

PROVEAN

Benign

1.6

REVEL

Benign

0.092

Sift

Benign

0.74

Sift4G

Benign

0.86

Polyphen

0.0020

Vest4

0.097

MVP

0.068

MPC

0.084

ClinPred

0.030

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.36

Mutation Taster

=90/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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