chr7-842045-C-T

Variant names:

• chr7-842045-C-T
• rs41273066
• NM_001130965.3:c.366C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001130965.3(SUN1):​c.366C>T​(p.Val122Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,614,188 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (12 hom., cov: 33)
  • Exomes 𝑓: 0.015 (229 hom.)
• Consequence: SUN1 NM_001130965.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.226
• Publications: 5 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 7-842045-C-T is Benign according to our data. Variant chr7-842045-C-T is described in ClinVar as Benign. ClinVar VariationId is 461660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.226 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0106 (1620/152306) while in subpopulation NFE AF = 0.0161 (1094/68032). AF 95% confidence interval is 0.0153. There are 12 homozygotes in GnomAd4. There are 774 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130965.3. 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.366C>T	p.Val122Val	synonymous	Exon 3 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367651.1		c.585C>T	p.Val195Val	synonymous	Exon 4 of 22	NP_001354580.1
	SUN1	NM_001367705.1		c.366C>T	p.Val122Val	synonymous	Exon 4 of 23	NP_001354634.1	O94901-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.366C>T	p.Val122Val	synonymous	Exon 3 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000457378.6	TSL:1	c.429C>T	p.Val143Val	synonymous	Exon 5 of 7	ENSP00000395952.2	O94901-7
	SUN1	ENST00000963118.1		c.366C>T	p.Val122Val	synonymous	Exon 4 of 24	ENSP00000633177.1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1620 AN: 152188 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.0116 AC: 2906 AN: 249522 AF XY: 0.0125

Gnomad AFR exome AF: 0.00362

Gnomad AMR exome AF: 0.00620

Gnomad ASJ exome AF: 0.00616

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0114

Gnomad NFE exome AF: 0.0149

Gnomad OTH exome AF: 0.0104

GnomAD4 exome AF: 0.0152 AC: 22192 AN: 1461882 Hom.: 229 Cov.: 33 AF XY: 0.0150 AC XY: 10941 AN XY: 727240

African (AFR) AF: 0.00209 AC: 70 AN: 33480

American (AMR) AF: 0.00633 AC: 283 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 158 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0189 AC: 1630 AN: 86258

European-Finnish (FIN) AF: 0.0117 AC: 626 AN: 53418

Middle Eastern (MID) AF: 0.00902 AC: 52 AN: 5768

European-Non Finnish (NFE) AF: 0.0166 AC: 18466 AN: 1112004

Other (OTH) AF: 0.0150 AC: 906 AN: 60396

GnomAD4 genome AF: 0.0106 AC: 1620 AN: 152306 Hom.: 12 Cov.: 33 AF XY: 0.0104 AC XY: 774 AN XY: 74470

African (AFR) AF: 0.00327 AC: 136 AN: 41558

American (AMR) AF: 0.0109 AC: 167 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0157 AC: 76 AN: 4826

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0161 AC: 1094 AN: 68032

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.0113 Hom.: 4

Bravo AF: 0.00989

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.0149

EpiControl AF: 0.0168

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Emery-Dreifuss muscular dystrophy (1)
-	-	1	SUN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.86
DANN	Benign	0.43
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs41273066; hg19: chr7-881682;