7-873223-C-T

Variant names:

• chr7-873223-C-T
• rs61741990
• NM_001130965.3:c.2250C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001367702.1(SUN1):​c.2257C>T​(p.Arg753*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,614,144 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0028 (11 hom.)
• Consequence: SUN1 NM_001367702.1 stop_gained
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.01

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 -12 ACMG points.

• BP6: Variant 7-873223-C-T is Benign according to our data. Variant chr7-873223-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 461654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN1	NM_001130965.3	c.2250C>T	p.Pro750Pro	synonymous_variant	Exon 19 of 19	ENST00000401592.6	NP_001124437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN1	ENST00000401592.6	c.2250C>T	p.Pro750Pro	synonymous_variant	Exon 19 of 19	1	NM_001130965.3	ENSP00000384015.1

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 290 AN: 152204 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00276

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00226 AC: 565 AN: 249476 Hom.: 3 AF XY: 0.00232 AC XY: 314 AN XY: 135376

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00167

Gnomad FIN exome AF: 0.00496

Gnomad NFE exome AF: 0.00257

Gnomad OTH exome AF: 0.00379

GnomAD4 exome AF: 0.00281 AC: 4111 AN: 1461822 Hom.: 11 Cov.: 31 AF XY: 0.00274 AC XY: 1991 AN XY: 727212

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.00248

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00157

Gnomad4 FIN exome AF: 0.00556

Gnomad4 NFE exome AF: 0.00308

Gnomad4 OTH exome AF: 0.00204

GnomAD4 genome AF: 0.00190 AC: 290 AN: 152322 Hom.: 0 Cov.: 34 AF XY: 0.00199 AC XY: 148 AN XY: 74484

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00396

Gnomad4 NFE AF: 0.00276

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00216 Hom.: 0

Bravo AF: 0.00161

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00218

EpiControl AF: 0.00190

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Emery-Dreifuss muscular dystrophy Benign:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SUN1: BP4, BP7 -

SUN1-related disorder Benign:1

Aug 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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	5.2
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs61741990; hg19: chr7-912860;