rs886041024
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_080675.4(SUN5):c.781G>A(p.Val261Met) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SUN5
NM_080675.4 missense
NM_080675.4 missense
Scores
6
9
2
Clinical Significance
Conservation
PhyloP100: 4.04
Genes affected
SUN5 (HGNC:16252): (Sad1 and UNC84 domain containing 5) The protein encoded by this gene appears to play a role in the meiotic stage of spermatogenesis. The encoded protein localizes to the junction between the sperm head and body and may be involved in nuclear envelope reconstitution and nuclear migration. Mutations in this gene have been implicated in acephalic spermatozoa syndrome. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
?
In a domain SUN (size 159) in uniprot entity SUN5_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_080675.4
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.86
PP5
?
Variant 20-32985852-C-T is Pathogenic according to our data. Variant chr20-32985852-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 268051.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUN5 | NM_080675.4 | c.781G>A | p.Val261Met | missense_variant | 11/13 | ENST00000356173.8 | |
SUN5 | XM_011528573.2 | c.850G>A | p.Val284Met | missense_variant | 12/14 | ||
SUN5 | XM_011528574.2 | c.706G>A | p.Val236Met | missense_variant | 10/12 | ||
SUN5 | XM_011528575.2 | c.511G>A | p.Val171Met | missense_variant | 9/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUN5 | ENST00000356173.8 | c.781G>A | p.Val261Met | missense_variant | 11/13 | 1 | NM_080675.4 | P2 | |
SUN5 | ENST00000375523.7 | c.706G>A | p.Val236Met | missense_variant | 10/12 | 5 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461824Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727228
GnomAD4 exome
AF:
AC:
1
AN:
1461824
Hom.:
Cov.:
35
AF XY:
AC XY:
1
AN XY:
727228
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Spermatogenic failure 16 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 07, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
1.0
.;D
Vest4
MutPred
0.64
.;Gain of sheet (P = 0.0827);
MVP
MPC
0.68
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at