Variant 7-48025933-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001030019.2(SUN3):c.128C>G(p.Thr43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)

Consequence

SUN3
NM_001030019.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08661336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUN3	NM_001030019.2 linkuse as main transcript	c.128C>G	p.Thr43Ser	missense_variant	2/10	ENST00000297325.9	NP_001025190.1	Q8TAQ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SUN3	ENST00000297325.9 linkuse as main transcript	c.128C>G	p.Thr43Ser	missense_variant	2/10	5	NM_001030019.2	ENSP00000297325.4	Q8TAQ9-1
SUN3	ENST00000395572.6 linkuse as main transcript	c.128C>G	p.Thr43Ser	missense_variant	3/11	1		ENSP00000378939.2	Q8TAQ9-1
SUN3	ENST00000412142.5 linkuse as main transcript	c.-7C>G		5_prime_UTR_variant	3/12	5		ENSP00000410204.2	Q8TAQ9-3
SUN3	ENST00000449896.2 linkuse as main transcript	n.128C>G		non_coding_transcript_exon_variant	2/11	2		ENSP00000395392.2	F8WDT4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000427

AC:

AN:

234048

Hom.:

AF XY:

0.00

AC XY:

AN XY:

126252

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000961

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000829

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2022

The c.128C>G (p.T43S) alteration is located in exon 2 (coding exon 2) of the SUN3 gene. This alteration results from a C to G substitution at nucleotide position 128, causing the threonine (T) at amino acid position 43 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.034

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.36

.;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.087

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.24

N;N

REVEL

Benign

0.034

Sift

Uncertain

0.022

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.42

B;B

Vest4

0.31

MutPred

0.23

Gain of disorder (P = 0.0447);Gain of disorder (P = 0.0447);

MVP

0.040

MPC

0.11

ClinPred

0.059

GERP RS

-1.6

Varity_R

0.042

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over