rs751489202

Variant names:

• chr7-48009041-A-C
• rs751489202
• NM_001030019.2:c.323T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001030019.2(SUN3):​c.323T>G​(p.Leu108Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L108P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SUN3 NM_001030019.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.89
• Publications: 0 publications found

Genes affected

SUN3 (HGNC:22429): (Sad1 and UNC84 domain containing 3) Predicted to enable protein-membrane adaptor activity. Predicted to be involved in nuclear envelope organization. Predicted to be integral component of nuclear inner membrane. Predicted to be part of meiotic nuclear membrane microtubule tethering complex. Predicted to be active in nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16670781).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001030019.2. 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
	SUN3	NM_001030019.2	MANE Select	c.323T>G	p.Leu108Arg	missense	Exon 4 of 10	NP_001025190.1	Q8TAQ9-1
	SUN3	NM_152782.4		c.323T>G	p.Leu108Arg	missense	Exon 5 of 11	NP_689995.3
	SUN3	NM_001284350.2		c.287T>G	p.Leu96Arg	missense	Exon 5 of 11	NP_001271279.1	Q8TAQ9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN3	ENST00000297325.9	TSL:5 MANE Select	c.323T>G	p.Leu108Arg	missense	Exon 4 of 10	ENSP00000297325.4	Q8TAQ9-1
	SUN3	ENST00000395572.6	TSL:1	c.323T>G	p.Leu108Arg	missense	Exon 5 of 11	ENSP00000378939.2	Q8TAQ9-1
	SUN3	ENST00000438771.5	TSL:1	c.23T>G	p.Leu8Arg	missense	Exon 1 of 8	ENSP00000409077.1	Q8TAQ9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 249680 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.000164

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460164 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 726308

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.0000225 AC: 1 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 85718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111422

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	0.017
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.11
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.31	T
Polyphen		0.76	P
Vest4		0.61
MutPred		0.43		Gain of MoRF binding (P = 0.0098)
MVP		0.32
MPC		0.13
ClinPred		0.54	D
GERP RS		4.5
PromoterAI		0.027	Neutral
Varity_R		0.50
gMVP		0.57
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs751489202; hg19: chr7-48048638;