rs200378884

Variant names:

• chr7-872520-G-A
• rs200378884
• NM_001130965.3:c.2199G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-872520-G-A
• chr7-872520-G-C
• chr7-872520-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001130965.3(SUN1):​c.2199G>A​(p.Thr733Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 1,603,006 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. T733T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (16 hom.)
• Consequence: SUN1 NM_001130965.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -4.45
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.064).
• BP6: Variant 7-872520-G-A is Benign according to our data. Variant chr7-872520-G-A is described in ClinVar as Benign. ClinVar VariationId is 461650.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.45 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 16 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130965.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	NM_001130965.3	MANE Select	c.2199G>A	p.Thr733Thr	synonymous	Exon 18 of 19	NP_001124437.1
	SUN1	NM_001367651.1		c.2613G>A	p.Thr871Thr	synonymous	Exon 21 of 22	NP_001354580.1
	SUN1	NM_001367705.1		c.2592G>A	p.Thr864Thr	synonymous	Exon 22 of 23	NP_001354634.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.2199G>A	p.Thr733Thr	synonymous	Exon 18 of 19	ENSP00000384015.1
	SUN1	ENST00000429178.5	TSL:1	c.1974G>A	p.Thr658Thr	synonymous	Exon 16 of 17	ENSP00000409909.1
	SUN1	ENST00000475971.5	TSL:1	n.2308G>A		non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 409 AN: 152128 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000918

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00338

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00299 AC: 683 AN: 228452 AF XY: 0.00309

Gnomad AFR exome AF: 0.000662

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.00881

Gnomad EAS exome AF: 0.0000591

Gnomad FIN exome AF: 0.00162

Gnomad NFE exome AF: 0.00419

Gnomad OTH exome AF: 0.00493

GnomAD4 exome AF: 0.00341 AC: 4949 AN: 1450760 Hom.: 16 Cov.: 31 AF XY: 0.00339 AC XY: 2441 AN XY: 720320

African (AFR) AF: 0.000659 AC: 22 AN: 33378

American (AMR) AF: 0.00181 AC: 78 AN: 43124

Ashkenazi Jewish (ASJ) AF: 0.00797 AC: 206 AN: 25840

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39412

South Asian (SAS) AF: 0.00156 AC: 131 AN: 83814

European-Finnish (FIN) AF: 0.00227 AC: 120 AN: 52812

Middle Eastern (MID) AF: 0.00434 AC: 25 AN: 5758

European-Non Finnish (NFE) AF: 0.00377 AC: 4174 AN: 1106622

Other (OTH) AF: 0.00315 AC: 189 AN: 60000

GnomAD4 genome AF: 0.00269 AC: 409 AN: 152246 Hom.: 1 Cov.: 32 AF XY: 0.00250 AC XY: 186 AN XY: 74452

African (AFR) AF: 0.000915 AC: 38 AN: 41530

American (AMR) AF: 0.00477 AC: 73 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00837 AC: 29 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4822

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00338 AC: 230 AN: 68012

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.00249 Hom.: 1

Bravo AF: 0.00259

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Emery-Dreifuss muscular dystrophy Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SUN1-related disorder Benign:1

Dec 16, 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.20
DANN	Benign	0.79
PhyloP100		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

dbSNP: rs200378884; hg19: chr7-912157;