17-4959850-C-A

Variant names:

• chr17-4959850-C-A
• rs768690755
• NM_004890.3:c.484G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004890.3(SPAG7):​c.484G>T​(p.Asp162Tyr) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D162N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPAG7 NM_004890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.77
• Publications: 0 publications found

Genes affected

SPAG7 (HGNC:11216): (sperm associated antigen 7) Predicted to enable nucleic acid binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SPAG7 Gene-Disease associations (from GenCC):

• PFAPA syndrome

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26975608).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004890.3. 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
	SPAG7	NM_004890.3	MANE Select	c.484G>T	p.Asp162Tyr	missense	Exon 6 of 7	NP_004881.2	O75391

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG7	ENST00000206020.8	TSL:1 MANE Select	c.484G>T	p.Asp162Tyr	missense	Exon 6 of 7	ENSP00000206020.3	O75391
	SPAG7	ENST00000575142.5	TSL:1	c.451G>T	p.Asp151Tyr	missense	Exon 6 of 6	ENSP00000461145.1	I3L4C3
	SPAG7	ENST00000859822.1		c.481G>T	p.Asp161Tyr	missense	Exon 6 of 7	ENSP00000529881.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.66	N
PhyloP100		4.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.11
Sift	Benign	0.19	T
Sift4G	Benign	0.20	T
Polyphen		0.88	P
Vest4		0.57
MutPred		0.25		Loss of ubiquitination at K164 (P = 0.0341)
MVP		0.13
MPC		1.4
ClinPred		0.94	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.41
gMVP		0.52

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: rs768690755; hg19: chr17-4863145;