7-832618-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001130965.3(SUN1):c.77+17A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,601,480 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0048 (27 hom.)
• Consequence: SUN1 NM_001130965.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.728

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-832618-A-T is Benign according to our data. Variant chr7-832618-A-T is described in ClinVar as [Benign]. Clinvar id is 1589741.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUN1	NM_001130965.3	c.77+17A>T		intron_variant		ENST00000401592.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUN1	ENST00000401592.6	c.77+17A>T		intron_variant		1	NM_001130965.3	P3

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 666 AN: 152168 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00444

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00532 AC: 1232 AN: 231550 Hom.: 6 AF XY: 0.00507 AC XY: 637 AN XY: 125566

Gnomad AFR exome AF: 0.000501

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.00834

Gnomad EAS exome AF: 0.000119

Gnomad SAS exome AF: 0.000600

Gnomad FIN exome AF: 0.0255

Gnomad NFE exome AF: 0.00509

Gnomad OTH exome AF: 0.00541

GnomAD4 exome AF: 0.00476 AC: 6900 AN: 1449194 Hom.: 27 Cov.: 30 AF XY: 0.00466 AC XY: 3353 AN XY: 720244

Gnomad4 AFR exome AF: 0.000301

Gnomad4 AMR exome AF: 0.00134

Gnomad4 ASJ exome AF: 0.00875

Gnomad4 EAS exome AF: 0.0000509

Gnomad4 SAS exome AF: 0.000769

Gnomad4 FIN exome AF: 0.0250

Gnomad4 NFE exome AF: 0.00443

Gnomad4 OTH exome AF: 0.00530

GnomAD4 genome AF: 0.00438 AC: 667 AN: 152286 Hom.: 2 Cov.: 33 AF XY: 0.00504 AC XY: 375 AN XY: 74462

Gnomad4 AFR AF: 0.000650

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.00444

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00433 Hom.: 0

Bravo AF: 0.00253

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Emery-Dreifuss muscular dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 21, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.8
Dann	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs143917535; hg19: chr7-872255;