rs116520953

chr7-843451-G-Achr7-843451-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001130965.3(SUN1):c.589G>A(p.Val197Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,614,176 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (14 hom., cov: 33)
  • Exomes 𝑓: 0.00068 (9 hom.)
• Consequence: SUN1 NM_001130965.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.360

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040222704).
• BP6: Variant 7-843451-G-A is Benign according to our data. Variant chr7-843451-G-A is described in ClinVar as [Benign]. Clinvar id is 530836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0058 (884/152356) while in subpopulation AFR AF= 0.0204 (850/41580). AF 95% confidence interval is 0.0193. There are 14 homozygotes in gnomad4. There are 425 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUN1	NM_001130965.3	c.589G>A	p.Val197Met	missense_variant	5/19	ENST00000401592.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUN1	ENST00000401592.6	c.589G>A	p.Val197Met	missense_variant	5/19	1	NM_001130965.3	P3

Frequencies

GnomAD3 genomes AF: 0.00580 AC: 883 AN: 152238 Hom.: 14 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00158 AC: 394 AN: 249072 Hom.: 4 AF XY: 0.00114 AC XY: 154 AN XY: 135282

Gnomad AFR exome AF: 0.0228

Gnomad AMR exome AF: 0.000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000797

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000682 AC: 997 AN: 1461820 Hom.: 9 Cov.: 33 AF XY: 0.000593 AC XY: 431 AN XY: 727214

Gnomad4 AFR exome AF: 0.0241

Gnomad4 AMR exome AF: 0.000872

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000468

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.00580 AC: 884 AN: 152356 Hom.: 14 Cov.: 33 AF XY: 0.00570 AC XY: 425 AN XY: 74500

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00231 Hom.: 1

Bravo AF: 0.00690

ESP6500AA AF: 0.0205 AC: 82

ESP6500EA AF: 0.000120 AC: 1

ExAC AF: 0.00195 AC: 236

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 26, 2024

- -

SUN1-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 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_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	1.8
Dann	Uncertain	1.0
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.80	T;.;T;T;T;T;T
MetaRNN	Benign	0.0040	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N;N
REVEL	Benign	0.022
Sift	Benign	0.085	T;T;T;T;T;T;T
Sift4G	Uncertain	0.039	D;T;T;T;D;T;T
Polyphen		0.58	.;P;.;.;.;P;.
Vest4		0.070
MVP		0.19
MPC		0.20
ClinPred		0.0061	T
GERP RS		-0.082
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.17

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: rs116520953; hg19: chr7-883088;