7-832463-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000457378.6(SUN1):c.44-42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,531,254 control chromosomes in the GnomAD database, including 17,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1956 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15936 hom.)
• Consequence: SUN1 ENST00000457378.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.575

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-832463-T-C is Benign according to our data. Variant chr7-832463-T-C is described in ClinVar as [Benign]. Clinvar id is 1252919.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUN1	NM_001130965.3			upstream_gene_variant		ENST00000401592.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUN1	ENST00000401592.6			upstream_gene_variant		1	NM_001130965.3	P3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23312 AN: 152104 Hom.: 1952 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0568

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.128

GnomAD3 exomes AF: 0.143 AC: 25884 AN: 181634 Hom.: 2242 AF XY: 0.135 AC XY: 13164 AN XY: 97216

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.228

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.000767

Gnomad SAS exome AF: 0.0631

Gnomad FIN exome AF: 0.199

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.146 AC: 200841 AN: 1379032 Hom.: 15936 Cov.: 24 AF XY: 0.143 AC XY: 97989 AN XY: 684526

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.000727

Gnomad4 SAS exome AF: 0.0634

Gnomad4 FIN exome AF: 0.196

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.153 AC: 23336 AN: 152222 Hom.: 1956 Cov.: 32 AF XY: 0.151 AC XY: 11267 AN XY: 74438

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0570

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.126

Alfa AF: 0.157 Hom.: 647

Bravo AF: 0.151

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.43
Dann	Benign	0.20

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: rs6952577; hg19: chr7-872100; COSMIC: COSV61778454; COSMIC: COSV61778454;