rs145390365

Variant names:

• chr7-838794-C-T
• rs145390365
• NM_001130965.3:c.78-4C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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.78-4C>T		splice_region intron	N/A	NP_001124437.1
	SUN1	NM_001367651.1		c.297-4C>T		splice_region intron	N/A	NP_001354580.1
	SUN1	NM_001367705.1		c.78-4C>T		splice_region intron	N/A	NP_001354634.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.78-4C>T		splice_region intron	N/A	ENSP00000384015.1
	SUN1	ENST00000457378.6	TSL:1	c.141-4C>T		splice_region intron	N/A	ENSP00000395952.2
	SUN1	ENST00000405266.5	TSL:5	c.78-4C>T		splice_region intron	N/A	ENSP00000384116.1

Frequencies

GnomAD3 genomes AF: 0.00573 AC: 872 AN: 152258 Hom.: 3 Cov.: 33

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

GnomAD2 exomes AF: 0.00813 AC: 1227 AN: 150886 AF XY: 0.00935

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 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.: 30 AF XY: 0.00789 AC XY: 5366 AN XY: 680388

African (AFR) AF: 0.00112 AC: 35 AN: 31280

American (AMR) AF: 0.00286 AC: 96 AN: 33620

Ashkenazi Jewish (ASJ) AF: 0.0148 AC: 363 AN: 24486

East Asian (EAS) AF: 0.00 AC: 0 AN: 35710

South Asian (SAS) AF: 0.0239 AC: 1838 AN: 77030

European-Finnish (FIN) AF: 0.00704 AC: 347 AN: 49256

Middle Eastern (MID) AF: 0.0282 AC: 159 AN: 5638

European-Non Finnish (NFE) AF: 0.00625 AC: 6685 AN: 1069338

Other (OTH) AF: 0.00859 AC: 494 AN: 57516

GnomAD4 genome AF: 0.00570 AC: 868 AN: 152376 Hom.: 3 Cov.: 33 AF XY: 0.00564 AC XY: 420 AN XY: 74518

African (AFR) AF: 0.00185 AC: 77 AN: 41602

American (AMR) AF: 0.00366 AC: 56 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0217 AC: 105 AN: 4832

European-Finnish (FIN) AF: 0.00706 AC: 75 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00725 AC: 493 AN: 68030

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00730 Hom.: 3

Bravo AF: 0.00491

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Emery-Dreifuss muscular dystrophy Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SUN1-related disorder Benign:1

Feb 20, 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	-0.78
CADD	Benign	5.2
DANN	Benign	0.51
PhyloP100		-0.35
PromoterAI		0.0034	Neutral
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs145390365; hg19: chr7-878431;