rs148795260

Variant names:

• chr20-32983821-G-C
• rs148795260
• NM_080675.4:c.1113C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-32983821-G-C
• chr20-32983821-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 5P and 2B. PM1 PM2 PP2 BP4_Moderate

The NM_080675.4(SUN5):​c.1113C>G​(p.His371Gln) variant causes a missense 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. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SUN5 NM_080675.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM1: In a topological_domain Perinuclear space (size 256) in uniprot entity SUN5_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_080675.4
• PM2: Very rare variant in population databases, with high coverage
• 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=0.07682663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN5	NM_080675.4	c.1113C>G	p.His371Gln	missense_variant	Exon 13 of 13	ENST00000356173.8	NP_542406.2
SUN5	XM_011528573.2	c.1182C>G	p.His394Gln	missense_variant	Exon 14 of 14		XP_011526875.1
SUN5	XM_011528574.2	c.1038C>G	p.His346Gln	missense_variant	Exon 12 of 12		XP_011526876.1
SUN5	XM_011528575.2	c.843C>G	p.His281Gln	missense_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.1113C>G	p.His371Gln	missense_variant	Exon 13 of 13	1	NM_080675.4	ENSP00000348496.3
SUN5	ENST00000375523.7	c.1038C>G	p.His346Gln	missense_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
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.6
DANN	Benign	0.88
DEOGEN2	Benign	0.0015	.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.34	T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	.;L
PhyloP100		1.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.027	D;D
Sift4G	Benign	0.15	T;T
Polyphen		0.023	.;B
Vest4		0.15
MutPred		0.13		.;Gain of solvent accessibility (P = 0.0081);
MVP		0.014
MPC		0.16
ClinPred		0.20	T
GERP RS		0.81
Varity_R		0.11
gMVP		0.16
Mutation Taster		=95/5	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: rs148795260; hg19: chr20-31571627;