rs76073621

chr7-838834-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001130965.3(SUN1):c.114G>A(p.Thr38=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00614 in 1,566,222 control chromosomes in the GnomAD database, including 543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (52 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (491 hom.)
• Consequence: SUN1 NM_001130965.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.800

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]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 7-838834-G-A is Benign according to our data. Variant chr7-838834-G-A is described in ClinVar as [Benign]. Clinvar id is 461639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUN1	NM_001130965.3	c.114G>A	p.Thr38=	synonymous_variant	2/19	ENST00000401592.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUN1	ENST00000401592.6	c.114G>A	p.Thr38=	synonymous_variant	2/19	1	NM_001130965.3	P3

Frequencies

GnomAD3 genomes AF: 0.00759 AC: 1155 AN: 152124 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.00525

GnomAD3 exomes AF: 0.0147 AC: 2640 AN: 180074 Hom.: 159 AF XY: 0.0141 AC XY: 1351 AN XY: 95752

Gnomad AFR exome AF: 0.000275

Gnomad AMR exome AF: 0.000473

Gnomad ASJ exome AF: 0.00333

Gnomad EAS exome AF: 0.150

Gnomad SAS exome AF: 0.00410

Gnomad FIN exome AF: 0.0206

Gnomad NFE exome AF: 0.00142

Gnomad OTH exome AF: 0.00670

GnomAD4 exome AF: 0.00598 AC: 8456 AN: 1413980 Hom.: 491 Cov.: 30 AF XY: 0.00604 AC XY: 4222 AN XY: 698708

Gnomad4 AFR exome AF: 0.000153

Gnomad4 AMR exome AF: 0.000409

Gnomad4 ASJ exome AF: 0.00294

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.00376

Gnomad4 FIN exome AF: 0.0202

Gnomad4 NFE exome AF: 0.000723

Gnomad4 OTH exome AF: 0.00824

GnomAD4 genome AF: 0.00760 AC: 1157 AN: 152242 Hom.: 52 Cov.: 33 AF XY: 0.00973 AC XY: 724 AN XY: 74428

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0242

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00239 Hom.: 0

Bravo AF: 0.00678

Asia WGS AF: 0.0580 AC: 201 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Emery-Dreifuss muscular dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

SUN1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 28, 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	-0.40
Cadd	Benign	3.6
Dann	Benign	0.88
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

Other links and lift over

dbSNP: rs76073621; hg19: chr7-878471; COSMIC: COSV61777726; COSMIC: COSV61777726;