rs886041024

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_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

Scores

6
10
3

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.04
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

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 Protein UniProt
SUN5NM_080675.4 linkc.781G>A p.Val261Met missense_variant 11/13 ENST00000356173.8 NP_542406.2 Q8TC36A0A384MDU5
SUN5XM_011528573.2 linkc.850G>A p.Val284Met missense_variant 12/14 XP_011526875.1
SUN5XM_011528574.2 linkc.706G>A p.Val236Met missense_variant 10/12 XP_011526876.1 A9Z1W8
SUN5XM_011528575.2 linkc.511G>A p.Val171Met missense_variant 9/11 XP_011526877.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SUN5ENST00000356173.8 linkc.781G>A p.Val261Met missense_variant 11/131 NM_080675.4 ENSP00000348496.3 Q8TC36
SUN5ENST00000375523.7 linkc.706G>A p.Val236Met missense_variant 10/125 ENSP00000364673.3 A9Z1W8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461824
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
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 providedliterature onlyOMIMNov 07, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.079
.;T
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.86
D;D
MetaSVM
Uncertain
0.49
D
MutationAssessor
Uncertain
2.0
.;M
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.3
N;N
REVEL
Uncertain
0.63
Sift
Uncertain
0.0090
D;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
1.0
.;D
Vest4
0.89
MutPred
0.64
.;Gain of sheet (P = 0.0827);
MVP
0.61
MPC
0.68
ClinPred
0.98
D
GERP RS
5.7
Varity_R
0.31
gMVP
0.60

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

LitVar

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

Other links and lift over

dbSNP: rs886041024; hg19: chr20-31573658; API