20-32983866-G-C

Variant names:

• chr20-32983866-G-C
• rs572445773
• NM_080675.4:c.1068C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_080675.4(SUN5):​c.1068C>G​(p.Arg356Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R356R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SUN5 NM_080675.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.69
• Publications: 2 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-3.69 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN5	NM_080675.4	c.1068C>G	p.Arg356Arg	synonymous_variant	Exon 13 of 13	ENST00000356173.8	NP_542406.2
SUN5	XM_011528573.2	c.1137C>G	p.Arg379Arg	synonymous_variant	Exon 14 of 14		XP_011526875.1
SUN5	XM_011528574.2	c.993C>G	p.Arg331Arg	synonymous_variant	Exon 12 of 12		XP_011526876.1
SUN5	XM_011528575.2	c.798C>G	p.Arg266Arg	synonymous_variant	Exon 11 of 11		XP_011526877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN5	ENST00000356173.8	c.1068C>G	p.Arg356Arg	synonymous_variant	Exon 13 of 13	1	NM_080675.4	ENSP00000348496.3
SUN5	ENST00000375523.7	c.993C>G	p.Arg331Arg	synonymous_variant	Exon 12 of 12	5		ENSP00000364673.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.60
PhyloP100		-3.7

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

Other links and lift over

dbSNP: rs572445773; hg19: chr20-31571672;