Genetic Variant NM_001030019.2:c.670A>G (chr7-47996054-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001030019.2(SUN3):c.670A>G(p.Met224Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000701 in 1,425,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M224L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SUN3
NM_001030019.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.75

Publications

1 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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23103413).

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.670A>G	p.Met224Val	missense	Exon 7 of 10	NP_001025190.1	Q8TAQ9-1
SUN3	NM_152782.4		c.670A>G	p.Met224Val	missense	Exon 8 of 11	NP_689995.3
SUN3	NM_001284350.2		c.634A>G	p.Met212Val	missense	Exon 8 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.670A>G	p.Met224Val	missense	Exon 7 of 10	ENSP00000297325.4	Q8TAQ9-1
SUN3	ENST00000395572.6	TSL:1	c.670A>G	p.Met224Val	missense	Exon 8 of 11	ENSP00000378939.2	Q8TAQ9-1
SUN3	ENST00000438771.5	TSL:1	c.370A>G	p.Met124Val	missense	Exon 4 of 8	ENSP00000409077.1	Q8TAQ9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1425574

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31236

American (AMR)

AF:

0.00

AC:

AN:

36380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25186

East Asian (EAS)

AF:

0.00

AC:

AN:

38500

South Asian (SAS)

AF:

0.00

AC:

AN:

78996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097664

Other (OTH)

AF:

0.0000170

AC:

AN:

58862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.018

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.78

M_CAP

Benign

0.0046

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.3

PhyloP100

4.8

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.3

REVEL

Benign

0.12

Sift

Benign

0.098

Sift4G

Benign

0.57

Polyphen

0.42

Vest4

0.39

MutPred

0.52

Loss of catalytic residue at M224 (P = 0.1155)

MVP

0.52

MPC

0.15

ClinPred

0.71

GERP RS

5.3

Varity_R

0.21

gMVP

0.44

Mutation Taster

=85/15

polymorphism

(source)

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

Publications

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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