7-873223-C-T

Variant names:

• chr7-873223-C-T
• rs61741990
• NM_001130965.3:c.2250C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001130965.3(SUN1):​c.2250C>T​(p.Pro750Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,614,144 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0028 (11 hom.)
• Consequence: SUN1 NM_001130965.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.01
• 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: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 7-873223-C-T is Benign according to our data. Variant chr7-873223-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 461654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.01 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 11 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	NM_001130965.3	MANE Select	c.2250C>T	p.Pro750Pro	synonymous	Exon 19 of 19	NP_001124437.1
	SUN1	NM_001367702.1		c.2257C>T	p.Arg753*	stop_gained	Exon 20 of 20	NP_001354631.1
	SUN1	NM_001367651.1		c.2664C>T	p.Pro888Pro	synonymous	Exon 22 of 22	NP_001354580.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN1	ENST00000401592.6	TSL:1 MANE Select	c.2250C>T	p.Pro750Pro	synonymous	Exon 19 of 19	ENSP00000384015.1
	SUN1	ENST00000429178.5	TSL:1	c.2025C>T	p.Pro675Pro	synonymous	Exon 17 of 17	ENSP00000409909.1
	SUN1	ENST00000475971.5	TSL:1	n.2359C>T		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 290 AN: 152204 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00276

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00226 AC: 565 AN: 249476 AF XY: 0.00232

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00496

Gnomad NFE exome AF: 0.00257

Gnomad OTH exome AF: 0.00379

GnomAD4 exome AF: 0.00281 AC: 4111 AN: 1461822 Hom.: 11 Cov.: 31 AF XY: 0.00274 AC XY: 1991 AN XY: 727212

African (AFR) AF: 0.000418 AC: 14 AN: 33476

American (AMR) AF: 0.00248 AC: 111 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00157 AC: 135 AN: 86252

European-Finnish (FIN) AF: 0.00556 AC: 297 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00308 AC: 3429 AN: 1111960

Other (OTH) AF: 0.00204 AC: 123 AN: 60392

GnomAD4 genome AF: 0.00190 AC: 290 AN: 152322 Hom.: 0 Cov.: 34 AF XY: 0.00199 AC XY: 148 AN XY: 74484

African (AFR) AF: 0.000385 AC: 16 AN: 41558

American (AMR) AF: 0.00255 AC: 39 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00396 AC: 42 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00276 AC: 188 AN: 68036

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00216 Hom.: 0

Bravo AF: 0.00161

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00218

EpiControl AF: 0.00190

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Emery-Dreifuss muscular dystrophy (1)
-	-	1	not provided (1)
-	-	1	SUN1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	5.2
DANN	Benign	0.61
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs61741990; hg19: chr7-912860;