7-839130-T-C

Variant names:

• chr7-839130-T-C
• rs1127460
• NM_001130965.3:c.266+144T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001367651.1(SUN1):​c.485+144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 711,780 control chromosomes in the GnomAD database, including 210,662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.78 (46045 hom., cov: 34)
  • Exomes 𝑓: 0.77 (164617 hom.)
• Consequence: SUN1 NM_001367651.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850
• Publications: 7 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=-1.0).
• BP6: Variant 7-839130-T-C is Benign according to our data. Variant chr7-839130-T-C is described in ClinVar as Benign. ClinVar VariationId is 1253189.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367651.1. 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.266+144T>C		intron	N/A	NP_001124437.1
	SUN1	NM_001367651.1		c.485+144T>C		intron	N/A	NP_001354580.1
	SUN1	NM_001367705.1		c.266+144T>C		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.266+144T>C		intron	N/A	ENSP00000384015.1
	SUN1	ENST00000457378.6	TSL:1	c.329+144T>C		intron	N/A	ENSP00000395952.2
	SUN1	ENST00000963118.1		c.266+144T>C		intron	N/A	ENSP00000633177.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 118133 AN: 152146 Hom.: 45990 Cov.: 34

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.753

GnomAD4 exome AF: 0.766 AC: 428324 AN: 559516 Hom.: 164617 Cov.: 8 AF XY: 0.766 AC XY: 214192 AN XY: 279802

African (AFR) AF: 0.750 AC: 10157 AN: 13540

American (AMR) AF: 0.851 AC: 8886 AN: 10444

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 9014 AN: 12556

East Asian (EAS) AF: 0.795 AC: 20793 AN: 26150

South Asian (SAS) AF: 0.739 AC: 17600 AN: 23820

European-Finnish (FIN) AF: 0.866 AC: 21486 AN: 24800

Middle Eastern (MID) AF: 0.727 AC: 1455 AN: 2002

European-Non Finnish (NFE) AF: 0.759 AC: 317547 AN: 418272

Other (OTH) AF: 0.766 AC: 21386 AN: 27932

GnomAD4 genome AF: 0.777 AC: 118249 AN: 152264 Hom.: 46045 Cov.: 34 AF XY: 0.781 AC XY: 58158 AN XY: 74456

African (AFR) AF: 0.754 AC: 31315 AN: 41528

American (AMR) AF: 0.830 AC: 12707 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2450 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4185 AN: 5186

South Asian (SAS) AF: 0.763 AC: 3676 AN: 4820

European-Finnish (FIN) AF: 0.878 AC: 9324 AN: 10614

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 52035 AN: 68016

Other (OTH) AF: 0.755 AC: 1598 AN: 2116

Alfa AF: 0.768 Hom.: 6198

Bravo AF: 0.771

Asia WGS AF: 0.826 AC: 2873 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.43
PhyloP100		-0.085
PromoterAI		-0.0096	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: rs1127460; hg19: chr7-878767;