Variant 20-33000076-A-G 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_080675.4(SUN5):c.338T>C(p.Phe113Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000311 in 1,608,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SUN5
NM_080675.4 missense, splice_region

Scores

Splicing: ADA: 0.3542

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

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 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=0.2567214).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUN5	NM_080675.4 linkuse as main transcript	c.338T>C	p.Phe113Ser	missense_variant, splice_region_variant	5/13	ENST00000356173.8	NP_542406.2	Q8TC36A0A384MDU5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SUN5	ENST00000356173.8 linkuse as main transcript	c.338T>C	p.Phe113Ser	missense_variant, splice_region_variant	5/13	1	NM_080675.4	ENSP00000348496.3	Q8TC36
SUN5	ENST00000420875.5 linkuse as main transcript	c.305T>C	p.Phe102Ser	missense_variant	5/5	3		ENSP00000400089.1	Q5TDX9
SUN5	ENST00000375519.2 linkuse as main transcript	c.271T>C	p.Ser91Pro	missense_variant	4/4	2		ENSP00000364669.2	Q5TDX8
SUN5	ENST00000375523.7 linkuse as main transcript	c.263T>C	p.Phe88Ser	missense_variant, splice_region_variant	4/12	5		ENSP00000364673.3	A9Z1W8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456822

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

723832

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.338T>C (p.F113S) alteration is located in exon 5 (coding exon 5) of the SUN5 gene. This alteration results from a T to C substitution at nucleotide position 338, causing the phenylalanine (F) at amino acid position 113 to be replaced by a serine (S). 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

Benign

0.29

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

.;T;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.071

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.69

N;N;D

REVEL

Benign

0.20

Sift

Benign

0.075

T;T;D

Sift4G

Uncertain

0.032

D;D;D

Polyphen

0.98

.;D;.

Vest4

0.63

MutPred

0.53

.;Loss of stability (P = 0.0304);.;

MVP

0.30

MPC

0.54

ClinPred

0.84

GERP RS

4.1

Varity_R

0.093

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.35

dbscSNV1_RF

Benign

0.49

SpliceAI score (max)

0.050

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over