rs138051124

Variant names:

• chr7-869482-A-G
• rs138051124
• NM_001130965.3:c.2114A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001130965.3(SUN1):​c.2114A>G​(p.Asn705Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000886 in 1,613,806 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. N705N) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0050 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (9 hom.)
• Consequence: SUN1 NM_001130965.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 4.14
• Publications: 3 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]

LOC124901568 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009526759).
• BP6: Variant 7-869482-A-G is Benign according to our data. Variant chr7-869482-A-G is described in ClinVar as Benign. ClinVar VariationId is 461648.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00504 (767/152244) while in subpopulation AFR AF = 0.0175 (725/41530). AF 95% confidence interval is 0.0164. There are 6 homozygotes in GnomAd4. There are 365 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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.2114A>G	p.Asn705Ser	missense	Exon 17 of 19	NP_001124437.1	O94901-8
	SUN1	NM_001367651.1		c.2528A>G	p.Asn843Ser	missense	Exon 20 of 22	NP_001354580.1
	SUN1	NM_001367705.1		c.2507A>G	p.Asn836Ser	missense	Exon 21 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.2114A>G	p.Asn705Ser	missense	Exon 17 of 19	ENSP00000384015.1	O94901-8
	SUN1	ENST00000429178.5	TSL:1	c.1889A>G	p.Asn630Ser	missense	Exon 15 of 17	ENSP00000409909.1	H0Y742
	SUN1	ENST00000475971.5	TSL:1	n.2223A>G		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes AF: 0.00505 AC: 768 AN: 152126 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00108 AC: 270 AN: 249206 AF XY: 0.000799

Gnomad AFR exome AF: 0.0163

Gnomad AMR exome AF: 0.000435

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000454 AC: 663 AN: 1461562 Hom.: 9 Cov.: 31 AF XY: 0.000373 AC XY: 271 AN XY: 727090

African (AFR) AF: 0.0159 AC: 533 AN: 33476

American (AMR) AF: 0.000671 AC: 30 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000523 AC: 3 AN: 5732

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111810

Other (OTH) AF: 0.00103 AC: 62 AN: 60374

GnomAD4 genome AF: 0.00504 AC: 767 AN: 152244 Hom.: 6 Cov.: 32 AF XY: 0.00490 AC XY: 365 AN XY: 74448

African (AFR) AF: 0.0175 AC: 725 AN: 41530

American (AMR) AF: 0.00157 AC: 24 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68004

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00202 Hom.: 7

Bravo AF: 0.00560

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0172 AC: 72

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00138 AC: 167

EpiCase AF: 0.0000545

EpiControl AF: 0.0000594

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
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0095	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.1
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.17
Sift	Benign	0.043	D
Sift4G	Benign	0.061	T
Polyphen		0.85	P
Vest4		0.21
MVP		0.23
MPC		1.5
ClinPred		0.039	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.79
Mutation Taster		=91/9	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: rs138051124; hg19: chr7-909119;