Genetic Variant NM_001030019.2:c.265G>A (chr7-48017285-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001030019.2(SUN3):c.265G>A(p.Gly89Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,446,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SUN3
NM_001030019.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.25

Publications

0 publications found

Variant links:

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]

SUN3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34940472).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUN3	NM_001030019.2	MANE Select	c.265G>A	p.Gly89Ser	missense	Exon 3 of 10	NP_001025190.1	Q8TAQ9-1
SUN3	NM_152782.4		c.265G>A	p.Gly89Ser	missense	Exon 4 of 11	NP_689995.3
SUN3	NM_001284350.2		c.229G>A	p.Gly77Ser	missense	Exon 4 of 11	NP_001271279.1	Q8TAQ9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUN3	ENST00000297325.9	TSL:5 MANE Select	c.265G>A	p.Gly89Ser	missense	Exon 3 of 10	ENSP00000297325.4	Q8TAQ9-1
SUN3	ENST00000395572.6	TSL:1	c.265G>A	p.Gly89Ser	missense	Exon 4 of 11	ENSP00000378939.2	Q8TAQ9-1
SUN3	ENST00000412142.5	TSL:5	c.229G>A	p.Gly77Ser	missense	Exon 5 of 12	ENSP00000410204.2	Q8TAQ9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

247082

AF XY:

0.00

show subpopulations

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:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000415

AC:

AN:

1446364

Hom.:

Cov.:

AF XY:

0.00000694

AC XY:

AN XY:

720054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33078

American (AMR)

AF:

0.00

AC:

AN:

43996

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25992

East Asian (EAS)

AF:

0.00

AC:

AN:

39488

South Asian (SAS)

AF:

0.00

AC:

AN:

84630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00000454

AC:

AN:

1100676

Other (OTH)

AF:

0.0000167

AC:

AN:

59884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Benign

-0.049

Eigen_PC

Benign

-0.035

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.80

M_CAP

Benign

0.0092

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

3.3

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.1

REVEL

Benign

0.066

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.53

MutPred

0.34

Gain of disorder (P = 0.056)

MVP

0.54

MPC

0.36

ClinPred

0.89

GERP RS

2.9

PromoterAI

-0.0030

Neutral

(source)

Varity_R

0.15

gMVP

0.51

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over