Variant 20-33001239-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000356173.8(SUN5):c.251C>T(p.Ala84Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,578,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

SUN5
ENST00000356173.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.509

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040274233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUN5	NM_080675.4 linkuse as main transcript	c.251C>T	p.Ala84Val	missense_variant	4/13	ENST00000356173.8	NP_542406.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SUN5	ENST00000356173.8 linkuse as main transcript	c.251C>T	p.Ala84Val	missense_variant	4/13	1	NM_080675.4	ENSP00000348496	P2
SUN5	ENST00000375523.7 linkuse as main transcript	c.176C>T	p.Ala59Val	missense_variant	3/12	5		ENSP00000364673	A2
SUN5	ENST00000420875.5 linkuse as main transcript	c.218C>T	p.Ala73Val	missense_variant	4/5	3		ENSP00000400089
SUN5	ENST00000375519.2 linkuse as main transcript	c.212-1104C>T		intron_variant		2		ENSP00000364669

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000101

AC:

AN:

197944

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

105466

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000241

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000243

AC:

346

AN:

1426150

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

164

AN XY:

705766

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000246

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:

0.000309

Gnomad4 OTH exome

AF:

0.000136

GnomAD4 genome

AF:

0.000151

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000500

AC:

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

Dec 15, 2022

The c.251C>T (p.A84V) alteration is located in exon 4 (coding exon 4) of the SUN5 gene. This alteration results from a C to T substitution at nucleotide position 251, causing the alanine (A) at amino acid position 84 to be replaced by a valine (V). 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

0.094

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

3.4

DANN

Benign

0.91

DEOGEN2

Benign

0.0035

.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.64

T;T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.60

N;N;D

REVEL

Benign

0.042

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.38

T;T;D

Polyphen

0.0020

.;B;.

Vest4

0.16

MVP

0.030

MPC

0.16

ClinPred

0.034

GERP RS

0.86

Varity_R

0.022

gMVP

0.35

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.

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