Variant rs373925818 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_001130965.3(SUN1):c.23T>A(p.Met8Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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. M8T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SUN1
NM_001130965.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0670

Variant links:

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]

SUN1 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=0.19317248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUN1	NM_001130965.3 linkuse as main transcript	c.23T>A	p.Met8Lys	missense_variant	1/19	ENST00000401592.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUN1	ENST00000401592.6 linkuse as main transcript	c.23T>A	p.Met8Lys	missense_variant	1/19	1	NM_001130965.3	P3	O94901-8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461220

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

Cadd

Benign

Dann

Benign

0.95

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.95

D;D;D;.;D;D;D;D;D;D;D

M_CAP

Benign

0.0045

MetaRNN

Benign

0.19

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;N;N;N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.5

D;N;D;D;D;D;D;D;N;N;D

REVEL

Benign

0.16

Sift

Uncertain

0.014

D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.021

D;T;D;D;D;D;D;D;D;D;D

Vest4

0.75

MutPred

0.24

.;Gain of ubiquitination at M8 (P = 0.0289);Gain of ubiquitination at M8 (P = 0.0289);Gain of ubiquitination at M8 (P = 0.0289);Gain of ubiquitination at M8 (P = 0.0289);Gain of ubiquitination at M8 (P = 0.0289);Gain of ubiquitination at M8 (P = 0.0289);Gain of ubiquitination at M8 (P = 0.0289);Gain of ubiquitination at M8 (P = 0.0289);Gain of ubiquitination at M8 (P = 0.0289);Gain of ubiquitination at M8 (P = 0.0289);

MVP

0.33

MPC

0.20

ClinPred

0.46

GERP RS

-0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

gMVP

0.37

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over