Variant 7-843468-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001130965.3(SUN1):c.606C>T(p.Pro202=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 1,614,052 control chromosomes in the GnomAD database, including 1,637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 123 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1514 hom. )

Consequence

SUN1
NM_001130965.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.83

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 7-843468-C-T is Benign according to our data. Variant chr7-843468-C-T is described in ClinVar as [Benign]. Clinvar id is 461662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.83 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0391 (5962/152322) while in subpopulation NFE AF= 0.0487 (3311/68034). AF 95% confidence interval is 0.0473. There are 123 homozygotes in gnomad4. There are 2883 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 123 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUN1	NM_001130965.3 linkuse as main transcript	c.606C>T	p.Pro202=	synonymous_variant	5/19	ENST00000401592.6	NP_001124437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUN1	ENST00000401592.6 linkuse as main transcript	c.606C>T	p.Pro202=	synonymous_variant	5/19	1	NM_001130965.3	ENSP00000384015	P3	O94901-8

Frequencies

GnomAD3 genomes

AF:

0.0392

AC:

5965

AN:

152204

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0324

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0297

Gnomad ASJ

AF:

0.0602

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.0466

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0487

Gnomad OTH

AF:

0.0377

GnomAD3 exomes

AF:

0.0370

AC:

9209

AN:

248884

Hom.:

238

AF XY:

0.0363

AC XY:

4915

AN XY:

135258

show subpopulations

Gnomad AFR exome

AF:

0.0354

Gnomad AMR exome

AF:

0.0194

Gnomad ASJ exome

AF:

0.0655

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00944

Gnomad FIN exome

AF:

0.0456

Gnomad NFE exome

AF:

0.0513

Gnomad OTH exome

AF:

0.0459

GnomAD4 exome

AF:

0.0430

AC:

62888

AN:

1461730

Hom.:

1514

Cov.:

AF XY:

0.0425

AC XY:

30876

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.0351

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.0658

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00916

Gnomad4 FIN exome

AF:

0.0478

Gnomad4 NFE exome

AF:

0.0476

Gnomad4 OTH exome

AF:

0.0409

GnomAD4 genome

AF:

0.0391

AC:

5962

AN:

152322

Hom.:

123

Cov.:

AF XY:

0.0387

AC XY:

2883

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0323

Gnomad4 AMR

AF:

0.0297

Gnomad4 ASJ

AF:

0.0602

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00786

Gnomad4 FIN

AF:

0.0466

Gnomad4 NFE

AF:

0.0487

Gnomad4 OTH

AF:

0.0373

Alfa

AF:

0.0462

Hom.:

Bravo

AF:

0.0382

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0531

EpiControl

AF:

0.0520

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

SUN1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 23, 2024

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

-0.74

CADD

Benign

2.3

DANN

Benign

0.73

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