Variant rs78842948 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001130965.3(SUN1):c.278A>C(p.Gln93Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0028 in 1,614,168 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 57 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 47 hom. )

Consequence

SUN1
NM_001130965.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 6.45

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038112998).

BP6

Variant 7-841957-A-C is Benign according to our data. Variant chr7-841957-A-C is described in ClinVar as [Benign]. Clinvar id is 461658.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2133/152340) while in subpopulation AFR AF= 0.0482 (2002/41574). AF 95% confidence interval is 0.0464. There are 57 homozygotes in gnomad4. There are 1029 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 57 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUN1	NM_001130965.3 linkuse as main transcript	c.278A>C	p.Gln93Pro	missense_variant	3/19	ENST00000401592.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUN1	ENST00000401592.6 linkuse as main transcript	c.278A>C	p.Gln93Pro	missense_variant	3/19	1	NM_001130965.3	P3	O94901-8

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2130

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00350

AC:

874

AN:

249398

Hom.:

AF XY:

0.00253

AC XY:

343

AN XY:

135348

show subpopulations

Gnomad AFR exome

AF:

0.0490

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00163

AC:

2387

AN:

1461828

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

1026

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0511

Gnomad4 AMR exome

AF:

0.00268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000269

Gnomad4 OTH exome

AF:

0.00369

GnomAD4 genome

AF:

0.0140

AC:

2133

AN:

152340

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1029

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0482

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00253

Hom.:

Bravo

AF:

0.0164

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0371

AC:

145

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.00421

AC:

509

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

SUN1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 02, 2019

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_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;.;.;.;T;.;T;T;.;.;.;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.081

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

D;.;T;T;T;D;D;D;D;D;D;D

MetaRNN

Benign

0.0038

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

.;.;M;.;.;.;.;.;M;M;.;.

MutationTaster

Benign

0.90

D;D;D;D;N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-5.3

D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.32

Sift

Uncertain

0.0070

D;D;T;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0070

D;T;T;D;D;D;D;T;T;D;T;D

Polyphen

1.0

.;D;.;.;.;.;.;.;.;.;D;.

Vest4

0.57

MVP

0.33

MPC

0.51

ClinPred

0.060

GERP RS

4.5

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over