Genetic Variant SUN1:p.Val122Val (chr7-842045-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001130965.3(SUN1):c.366C>T(p.Val122Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,614,188 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 12 hom., cov: 33)

Exomes 𝑓: 0.015 ( 229 hom. )

Consequence

SUN1
NM_001130965.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.226

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 7-842045-C-T is Benign according to our data. Variant chr7-842045-C-T is described in ClinVar as [Benign]. Clinvar id is 461660.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.226 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0106 (1620/152306) while in subpopulation NFE AF= 0.0161 (1094/68032). AF 95% confidence interval is 0.0153. There are 12 homozygotes in gnomad4. There are 774 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN1	NM_001130965.3 link	c.366C>T	p.Val122Val	synonymous_variant	Exon 3 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.366C>T	p.Val122Val	synonymous_variant	Exon 3 of 19	1	NM_001130965.3	ENSP00000384015.1		O94901-8

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1620

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0155

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0161

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.0116

AC:

2906

AN:

249522

Hom.:

AF XY:

0.0125

AC XY:

1693

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.00362

Gnomad AMR exome

AF:

0.00620

Gnomad ASJ exome

AF:

0.00616

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0188

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.0149

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.0152

AC:

22192

AN:

1461882

Hom.:

229

Cov.:

AF XY:

0.0150

AC XY:

10941

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.00633

Gnomad4 ASJ exome

AF:

0.00605

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0189

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.0166

Gnomad4 OTH exome

AF:

0.0150

GnomAD4 genome

AF:

0.0106

AC:

1620

AN:

152306

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

774

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00327

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0157

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.0161

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.00989

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0168

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy

Benign:1

Jan 29, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.86

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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