20-32983844-C-T

Variant names:

• chr20-32983844-C-T
• rs151243035
• NM_080675.4:c.1090G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP2 BP4_Strong

The NM_080675.4(SUN5):​c.1090G>A​(p.Ala364Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,438,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A364S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: SUN5 NM_080675.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252
• Publications: 0 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.

• 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.
• BP4: Computational evidence support a benign effect (MetaRNN=0.024610639).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080675.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN5	NM_080675.4	MANE Select	c.1090G>A	p.Ala364Thr	missense	Exon 13 of 13	NP_542406.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUN5	ENST00000356173.8	TSL:1 MANE Select	c.1090G>A	p.Ala364Thr	missense	Exon 13 of 13	ENSP00000348496.3	Q8TC36
	SUN5	ENST00000375523.7	TSL:5	c.1015G>A	p.Ala339Thr	missense	Exon 12 of 12	ENSP00000364673.3	A9Z1W8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000377 AC: 9 AN: 238602 AF XY: 0.0000698

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000250 AC: 36 AN: 1438626 Hom.: 0 Cov.: 31 AF XY: 0.0000364 AC XY: 26 AN XY: 713862

African (AFR) AF: 0.00 AC: 0 AN: 32842

American (AMR) AF: 0.00 AC: 0 AN: 42104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25882

East Asian (EAS) AF: 0.00 AC: 0 AN: 38100

South Asian (SAS) AF: 0.000418 AC: 34 AN: 81354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099904

Other (OTH) AF: 0.0000336 AC: 2 AN: 59482

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000577 AC: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.15
DANN	Benign	0.33
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00091	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.26	N
PhyloP100		-0.25
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.80	N
REVEL	Benign	0.031
Sift	Benign	0.60	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.14		Gain of glycosylation at A364 (P = 0.0197)
MVP		0.014
MPC		0.15
ClinPred		0.038	T
GERP RS		-1.1
Varity_R		0.022
gMVP		0.27
Mutation Taster		=81/19	polymorphism

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: rs151243035; hg19: chr20-31571650;