rs886041025

Positions:

• chr20-32985782-G-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_080675.4(SUN5):​c.851C>G​(p.Ser284Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUN5 NM_080675.4 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.71

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 20-32985782-G-C is Pathogenic according to our data. Variant chr20-32985782-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 268052.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUN5	NM_080675.4	c.851C>G	p.Ser284Ter	stop_gained	11/13	ENST00000356173.8	NP_542406.2
SUN5	XM_011528573.2	c.920C>G	p.Ser307Ter	stop_gained	12/14		XP_011526875.1
SUN5	XM_011528574.2	c.776C>G	p.Ser259Ter	stop_gained	10/12		XP_011526876.1
SUN5	XM_011528575.2	c.581C>G	p.Ser194Ter	stop_gained	9/11		XP_011526877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUN5	ENST00000356173.8	c.851C>G	p.Ser284Ter	stop_gained	11/13	1	NM_080675.4	ENSP00000348496	P2
SUN5	ENST00000375523.7	c.776C>G	p.Ser259Ter	stop_gained	10/12	5		ENSP00000364673	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 16 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 07, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	41
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Uncertain	0.97	D
MutationTaster	Benign	1.0	A;A
Vest4		0.93
GERP RS		5.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs886041025; hg19: chr20-31573588;