20-32987751-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM1PP2

The NM_080675.4(SUN5):c.638C>T(p.Thr213Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,613,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

SUN5
NM_080675.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

Publications

2 publications found

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]

SUN5 Gene-Disease associations (from GenCC):

spermatogenic failure 16
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

SUN5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM1

In a topological_domain Perinuclear space (size 256) in uniprot entity SUN5_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_080675.4

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.68847 (below the threshold of 3.09). Trascript score misZ: 0.63256 (below the threshold of 3.09). GenCC associations: The gene is linked to spermatogenic failure 16.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN5	NM_080675.4 link	c.638C>T	p.Thr213Met	missense_variant	Exon 10 of 13	ENST00000356173.8	NP_542406.2	Q8TC36A0A384MDU5
SUN5	XM_011528573.2 link	c.707C>T	p.Thr236Met	missense_variant	Exon 11 of 14		XP_011526875.1
SUN5	XM_011528574.2 link	c.563C>T	p.Thr188Met	missense_variant	Exon 9 of 12		XP_011526876.1	A9Z1W8
SUN5	XM_011528575.2 link	c.368C>T	p.Thr123Met	missense_variant	Exon 8 of 11		XP_011526877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN5	ENST00000356173.8 link	c.638C>T	p.Thr213Met	missense_variant	Exon 10 of 13	1	NM_080675.4	ENSP00000348496.3		Q8TC36
SUN5	ENST00000375523.7 link	c.563C>T	p.Thr188Met	missense_variant	Exon 9 of 12	5		ENSP00000364673.3		A9Z1W8

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152018

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:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000682

AC:

AN:

249370

AF XY:

0.0000964

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1461020

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

726636

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.0000672

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.000373

AC:

AN:

85830

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1111730

Other (OTH)

AF:

0.0000331

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41498

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000416

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.638C>T (p.T213M) alteration is located in exon 10 (coding exon 10) of the SUN5 gene. This alteration results from a C to T substitution at nucleotide position 638, causing the threonine (T) at amino acid position 213 to be replaced by a methionine (M). 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

Pathogenic

0.79

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

.;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Benign

-0.86

MutationAssessor

Pathogenic

3.0

.;M

PhyloP100

4.0

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.8

D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

.;D

Vest4

0.75

MutPred

0.75

.;Loss of disorder (P = 0.0858);

MVP

0.21

MPC

0.65

ClinPred

0.91

GERP RS

5.0

Varity_R

0.23

gMVP

0.75

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

20-32987751-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over