rs113652875

Variant names:

• chr7-843468-C-T
• rs113652875
• NM_001130965.3:c.606C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001367658.1(SUN1):​c.-156C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 1,614,052 control chromosomes in the GnomAD database, including 1,637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (123 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1514 hom.)
• Consequence: SUN1 NM_001367658.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.83
• Publications: 12 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.056).
• BP6: Variant 7-843468-C-T is Benign according to our data. Variant chr7-843468-C-T is described in ClinVar as Benign. ClinVar VariationId is 461662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0391 (5962/152322) while in subpopulation NFE AF = 0.0487 (3311/68034). AF 95% confidence interval is 0.0473. There are 123 homozygotes in GnomAd4. There are 2883 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 123 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367658.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	NM_001130965.3	MANE Select	c.606C>T	p.Pro202Pro	synonymous	Exon 5 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367658.1		c.-156C>T		5_prime_UTR_premature_start_codon_gain	Exon 5 of 20	NP_001354587.1
	SUN1	NM_001367635.1		c.149C>T	p.Pro50Leu	missense	Exon 6 of 21	NP_001354564.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.606C>T	p.Pro202Pro	synonymous	Exon 5 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000429178.5	TSL:1	c.99C>T	p.Pro33Pro	synonymous	Exon 1 of 17	ENSP00000409909.1	H0Y742
	SUN1	ENST00000457378.6	TSL:1	c.669C>T	p.Pro223Pro	synonymous	Exon 7 of 7	ENSP00000395952.2	O94901-7

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5965 AN: 152204 Hom.: 123 Cov.: 33

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00786

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.0377

GnomAD2 exomes AF: 0.0370 AC: 9209 AN: 248884 AF XY: 0.0363

Gnomad AFR exome AF: 0.0354

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0655

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.0456

Gnomad NFE exome AF: 0.0513

Gnomad OTH exome AF: 0.0459

GnomAD4 exome AF: 0.0430 AC: 62888 AN: 1461730 Hom.: 1514 Cov.: 34 AF XY: 0.0425 AC XY: 30876 AN XY: 727162

African (AFR) AF: 0.0351 AC: 1174 AN: 33480

American (AMR) AF: 0.0212 AC: 949 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0658 AC: 1719 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.00916 AC: 790 AN: 86256

European-Finnish (FIN) AF: 0.0478 AC: 2551 AN: 53376

Middle Eastern (MID) AF: 0.0472 AC: 272 AN: 5768

European-Non Finnish (NFE) AF: 0.0476 AC: 52962 AN: 1111912

Other (OTH) AF: 0.0409 AC: 2467 AN: 60382

GnomAD4 genome AF: 0.0391 AC: 5962 AN: 152322 Hom.: 123 Cov.: 33 AF XY: 0.0387 AC XY: 2883 AN XY: 74502

African (AFR) AF: 0.0323 AC: 1342 AN: 41558

American (AMR) AF: 0.0297 AC: 455 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00786 AC: 38 AN: 4832

European-Finnish (FIN) AF: 0.0466 AC: 495 AN: 10618

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0487 AC: 3311 AN: 68034

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.0460 Hom.: 87

Bravo AF: 0.0382

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.0531

EpiControl AF: 0.0520

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Emery-Dreifuss muscular dystrophy (1)
-	-	1	not provided (1)
-	-	1	SUN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.3
DANN	Benign	0.73
PhyloP100		-1.8
PromoterAI		0.020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs113652875; hg19: chr7-883105; COSMIC: COSV61778265; COSMIC: COSV61778265;