Genetic Variant NM_001130965.3:c.13C>T (chr7-832537-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001130965.3(SUN1):c.13C>T(p.Arg5Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,613,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

SUN1
NM_001130965.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.93

Publications

2 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18563432).

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.13C>T	p.Arg5Trp	missense	Exon 1 of 19	NP_001124437.1	O94901-8
SUN1	NM_001367635.1		c.-445C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 21	NP_001354564.1
SUN1	NM_001367705.1		c.13C>T	p.Arg5Trp	missense	Exon 2 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.13C>T	p.Arg5Trp	missense	Exon 1 of 19	ENSP00000384015.1	O94901-8
SUN1	ENST00000457378.6	TSL:1	c.76C>T	p.Arg26Trp	missense	Exon 3 of 7	ENSP00000395952.2	O94901-7
SUN1	ENST00000425407.6	TSL:5	c.-138C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	ENSP00000392309.2	O94901-5

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000324

AC:

AN:

247258

AF XY:

0.0000446

show subpopulations

Gnomad AFR exome

AF:

0.000327

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1460956

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726636

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

33476

American (AMR)

AF:

0.0000224

AC:

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000810

AC:

AN:

1111568

Other (OTH)

AF:

0.0000497

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000204

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41560

American (AMR)

AF:

0.000131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000153

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.000638

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000664

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

Uncertain

0.45

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.034

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.90

PhyloP100

2.9

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.3

REVEL

Uncertain

0.35

Sift

Benign

0.039

Sift4G

Uncertain

0.051

Vest4

0.64

MVP

0.24

MPC

0.44

ClinPred

0.47

GERP RS

4.9

PromoterAI

0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.37

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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