rs200907784
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001130965.3(SUN1):c.2143G>A(p.Val715Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,612,934 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00075 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00080 ( 2 hom. )
Consequence
SUN1
NM_001130965.3 missense
NM_001130965.3 missense
Scores
1
4
10
Clinical Significance
Conservation
PhyloP100: 9.69
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.044427216).
BP6
?
Variant 7-869511-G-A is Benign according to our data. Variant chr7-869511-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 461649.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
BS2
?
High Homozygotes in GnomAdExome4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUN1 | NM_001130965.3 | c.2143G>A | p.Val715Ile | missense_variant | 17/19 | ENST00000401592.6 | |
LOC124901568 | XR_007060177.1 | n.282-1818C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUN1 | ENST00000401592.6 | c.2143G>A | p.Val715Ile | missense_variant | 17/19 | 1 | NM_001130965.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000749 AC: 114AN: 152102Hom.: 1 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000837 AC: 208AN: 248452Hom.: 1 AF XY: 0.000928 AC XY: 125AN XY: 134766
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GnomAD4 exome AF: 0.000804 AC: 1175AN: 1460714Hom.: 2 Cov.: 31 AF XY: 0.000884 AC XY: 642AN XY: 726614
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GnomAD4 genome ? AF: 0.000749 AC: 114AN: 152220Hom.: 1 Cov.: 32 AF XY: 0.000672 AC XY: 50AN XY: 74440
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 26, 2022 | The c.2143G>A (p.V715I) alteration is located in exon 17 (coding exon 17) of the SUN1 gene. This alteration results from a G to A substitution at nucleotide position 2143, causing the valine (V) at amino acid position 715 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Emery-Dreifuss muscular dystrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | - - |
SUN1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 09, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
D;.;.;.;D;.
Vest4
MVP
MPC
1.5
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at