rs142172157

Variant names:

• chr20-32985184-C-A
• NM_080675.4:c.899G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-32985184-C-A
• chr20-32985184-C-G
• chr20-32985184-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_080675.4(SUN5):​c.899G>T​(p.Gly300Val) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUN5 NM_080675.4 missense, splice_region
• Scores: Splicing: ADA: 0.5945
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.876

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUN5	NM_080675.4	c.899G>T	p.Gly300Val	missense_variant, splice_region_variant	Exon 12 of 13	ENST00000356173.8	NP_542406.2
SUN5	XM_011528573.2	c.968G>T	p.Gly323Val	missense_variant, splice_region_variant	Exon 13 of 14		XP_011526875.1
SUN5	XM_011528574.2	c.824G>T	p.Gly275Val	missense_variant, splice_region_variant	Exon 11 of 12		XP_011526876.1
SUN5	XM_011528575.2	c.629G>T	p.Gly210Val	missense_variant, splice_region_variant	Exon 10 of 11		XP_011526877.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUN5	ENST00000356173.8	c.899G>T	p.Gly300Val	missense_variant, splice_region_variant	Exon 12 of 13	1	NM_080675.4	ENSP00000348496.3
SUN5	ENST00000375523.7	c.824G>T	p.Gly275Val	missense_variant, splice_region_variant	Exon 11 of 12	5		ENSP00000364673.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	.;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.81	T;T
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-7.7	D;D
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	.;D
Vest4		0.94
MutPred		0.54		.;Loss of disorder (P = 0.0825);
MVP		0.58
MPC		0.76
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.77
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.59
dbscSNV1_RF	Benign	0.57
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-31572990;