7-851463-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001130965.3(SUN1):c.738G>T(p.Trp246Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 1,607,702 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 115 hom. )

Consequence

SUN1
NM_001130965.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.23

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006855428).

BP6

Variant 7-851463-G-T is Benign according to our data. Variant chr7-851463-G-T is described in ClinVar as [Benign]. Clinvar id is 461666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00572 (871/152324) while in subpopulation SAS AF= 0.0216 (104/4824). AF 95% confidence interval is 0.0182. There are 3 homozygotes in gnomad4. There are 421 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN1	NM_001130965.3 link	c.738G>T	p.Trp246Cys	missense_variant	Exon 6 of 19	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.738G>T	p.Trp246Cys	missense_variant	Exon 6 of 19	1	NM_001130965.3	ENSP00000384015.1		O94901-8

Frequencies

GnomAD3 genomes

AF:

0.00575

AC:

875

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0222

Gnomad FIN

AF:

0.00706

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00725

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00791

AC:

1864

AN:

235506

Hom.:

AF XY:

0.00908

AC XY:

1164

AN XY:

128144

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.0148

Gnomad EAS exome

AF:

0.0000578

Gnomad SAS exome

AF:

0.0233

Gnomad FIN exome

AF:

0.00715

Gnomad NFE exome

AF:

0.00702

Gnomad OTH exome

AF:

0.00776

GnomAD4 exome

AF:

0.00732

AC:

10656

AN:

1455378

Hom.:

115

Cov.:

AF XY:

0.00802

AC XY:

5802

AN XY:

723234

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00304

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0239

Gnomad4 FIN exome

AF:

0.00702

Gnomad4 NFE exome

AF:

0.00631

Gnomad4 OTH exome

AF:

0.00867

GnomAD4 genome

AF:

0.00572

AC:

871

AN:

152324

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

421

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0216

Gnomad4 FIN

AF:

0.00706

Gnomad4 NFE

AF:

0.00725

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00705

Hom.:

Bravo

AF:

0.00495

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.000957

AC:

ESP6500EA

AF:

0.00740

AC:

ExAC

AF:

0.00789

AC:

951

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SUN1-related disorder

Benign:1

Feb 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SUN1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.089

T;.;T

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

T;T;T

MetaRNN

Benign

0.0069

T;T;T

MetaSVM

Benign

-0.73

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-7.6

D;D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Vest4

0.82

MVP

0.31

MPC

0.57

ClinPred

0.026

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.68

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