Variant 7-838794-C-T 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.78-4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00709 in 1,536,250 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0072 ( 110 hom. )

Consequence

SUN1
NM_001130965.3 splice_region, intron

Scores

Splicing: ADA: 0.00002075

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.352

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:

SUN1 (HGNC:):

SUN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 7-838794-C-T is Benign according to our data. Variant chr7-838794-C-T is described in ClinVar as [Benign]. Clinvar id is 461669.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0057 (868/152376) while in subpopulation SAS AF= 0.0217 (105/4832). AF 95% confidence interval is 0.0184. There are 3 homozygotes in gnomad4. There are 420 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/exons	MANE	Protein	UniProt
SUN1	NM_001130965.3 linkuse as main transcript	c.78-4C>T		splice_region_variant, intron_variant		ENST00000401592.6	NP_001124437.1	O94901-8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUN1	ENST00000401592.6 linkuse as main transcript	c.78-4C>T		splice_region_variant, intron_variant		1	NM_001130965.3	ENSP00000384015.1		O94901-8

Frequencies

GnomAD3 genomes

AF:

0.00573

AC:

872

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00366

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0223

Gnomad FIN

AF:

0.00706

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00725

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00813

AC:

1227

AN:

150886

Hom.:

AF XY:

0.00935

AC XY:

741

AN XY:

79214

show subpopulations

Gnomad AFR exome

AF:

0.000824

Gnomad AMR exome

AF:

0.00259

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0233

Gnomad FIN exome

AF:

0.00752

Gnomad NFE exome

AF:

0.00692

Gnomad OTH exome

AF:

0.00752

GnomAD4 exome

AF:

0.00724

AC:

10017

AN:

1383874

Hom.:

110

Cov.:

AF XY:

0.00789

AC XY:

5366

AN XY:

680388

show subpopulations

Gnomad4 AFR exome

AF:

0.00112

Gnomad4 AMR exome

AF:

0.00286

Gnomad4 ASJ exome

AF:

0.0148

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0239

Gnomad4 FIN exome

AF:

0.00704

Gnomad4 NFE exome

AF:

0.00625

Gnomad4 OTH exome

AF:

0.00859

GnomAD4 genome

AF:

0.00570

AC:

868

AN:

152376

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

420

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00366

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0217

Gnomad4 FIN

AF:

0.00706

Gnomad4 NFE

AF:

0.00725

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00730

Hom.:

Bravo

AF:

0.00491

Asia WGS

AF:

0.00520

AC:

AN:

3478

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

Feb 20, 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_noAF

Benign

-0.78

CADD

Benign

5.2

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.016

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