rs377094306

Variant names:

• chr7-851458-C-G
• rs377094306
• NM_001130965.3:c.733C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-851458-C-G
• chr7-851458-C-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001130965.3(SUN1):​c.733C>G​(p.Leu245Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,608,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: SUN1 NM_001130965.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.29
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05062887).

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.733C>G	p.Leu245Val	missense	Exon 6 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367651.1		c.1147C>G	p.Leu383Val	missense	Exon 9 of 22	NP_001354580.1
	SUN1	NM_001367705.1		c.1126C>G	p.Leu376Val	missense	Exon 10 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.733C>G	p.Leu245Val	missense	Exon 6 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000429178.5	TSL:1	c.508C>G	p.Leu170Val	missense	Exon 4 of 17	ENSP00000409909.1	H0Y742
	SUN1	ENST00000963118.1		c.1126C>G	p.Leu376Val	missense	Exon 10 of 24	ENSP00000633177.1

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000169 AC: 40 AN: 237230 AF XY: 0.000124

Gnomad AFR exome AF: 0.000986

Gnomad AMR exome AF: 0.000329

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000480

Gnomad NFE exome AF: 0.000112

Gnomad OTH exome AF: 0.000343

GnomAD4 exome AF: 0.000130 AC: 190 AN: 1456374 Hom.: 0 Cov.: 32 AF XY: 0.000123 AC XY: 89 AN XY: 723834

African (AFR) AF: 0.000629 AC: 21 AN: 33412

American (AMR) AF: 0.000432 AC: 19 AN: 43988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25976

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.00 AC: 0 AN: 84940

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 53038

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5756

European-Non Finnish (NFE) AF: 0.000109 AC: 121 AN: 1109564

Other (OTH) AF: 0.000349 AC: 21 AN: 60152

GnomAD4 genome AF: 0.000342 AC: 52 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23 AN XY: 74356

African (AFR) AF: 0.000748 AC: 31 AN: 41438

American (AMR) AF: 0.000720 AC: 11 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000676 Hom.: 0

Bravo AF: 0.000382

ESP6500AA AF: 0.000638 AC: 2

ESP6500EA AF: 0.000279 AC: 2

ExAC AF: 0.000182 AC: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Emery-Dreifuss muscular dystrophy (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.85	T
PhyloP100		2.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.061
Sift	Benign	0.043	D
Sift4G	Benign	0.12	T
Vest4		0.30
MVP		0.15
MPC		0.40
ClinPred		0.039	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.30
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs377094306; hg19: chr7-891095; COSMIC: COSV100568880; COSMIC: COSV100568880;