rs143543329

Variant names:

• chr7-872560-C-T
• rs143543329
• NM_001130965.3:c.2239C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-872560-C-T
• chr7-872560-C-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001130965.3(SUN1):​c.2239C>T​(p.Leu747Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000302 in 1,578,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: SUN1 NM_001130965.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.08896
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.91
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.054).
• BP6: Variant 7-872560-C-T is Benign according to our data. Variant chr7-872560-C-T is described in ClinVar as Benign. ClinVar VariationId is 461653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.91 with no splicing effect.

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.2239C>T	p.Leu747Leu	splice_region synonymous	Exon 18 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367651.1		c.2653C>T	p.Leu885Leu	splice_region synonymous	Exon 21 of 22	NP_001354580.1
	SUN1	NM_001367705.1		c.2632C>T	p.Leu878Leu	splice_region synonymous	Exon 22 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.2239C>T	p.Leu747Leu	splice_region synonymous	Exon 18 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000429178.5	TSL:1	c.2014C>T	p.Leu672Leu	splice_region synonymous	Exon 16 of 17	ENSP00000409909.1	H0Y742
	SUN1	ENST00000475971.5	TSL:1	n.2348C>T		splice_region non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 221 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00512

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000417 AC: 78 AN: 186882 AF XY: 0.000340

Gnomad AFR exome AF: 0.00629

Gnomad AMR exome AF: 0.000326

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000126

Gnomad OTH exome AF: 0.000202

GnomAD4 exome AF: 0.000177 AC: 253 AN: 1426060 Hom.: 0 Cov.: 30 AF XY: 0.000149 AC XY: 105 AN XY: 705836

African (AFR) AF: 0.00633 AC: 208 AN: 32856

American (AMR) AF: 0.000333 AC: 13 AN: 39056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25426

East Asian (EAS) AF: 0.00 AC: 0 AN: 38216

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51236

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5696

European-Non Finnish (NFE) AF: 0.00000640 AC: 7 AN: 1093376

Other (OTH) AF: 0.000389 AC: 23 AN: 59064

GnomAD4 genome AF: 0.00146 AC: 223 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.00136 AC XY: 101 AN XY: 74470

African (AFR) AF: 0.00515 AC: 214 AN: 41538

American (AMR) AF: 0.000262 AC: 4 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.0000671 Hom.: 0

Bravo AF: 0.00190

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	5.3
DANN	Benign	0.65
PhyloP100		1.9
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.089
dbscSNV1_RF	Benign	0.34
Splicevardb		1.0
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: rs143543329; hg19: chr7-912197;