chr17-4959545-G-C

Variant names:

• chr17-4959545-G-C
• rs768735296
• NM_004890.3:c.673C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004890.3(SPAG7):​c.673C>G​(p.Pro225Ala) 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. 16/21 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. P225S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPAG7 NM_004890.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057204366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG7	NM_004890.3	c.673C>G	p.Pro225Ala	missense_variant	Exon 7 of 7	ENST00000206020.8	NP_004881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG7	ENST00000206020.8	c.673C>G	p.Pro225Ala	missense_variant	Exon 7 of 7	1	NM_004890.3	ENSP00000206020.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.015	T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.14	N;.
PhyloP100		0.52
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.10	N;.
REVEL	Benign	0.050
Sift	Benign	0.26	T;.
Sift4G	Benign	0.079	T;T
Polyphen		0.049	B;.
Vest4		0.20
MutPred		0.12		Loss of catalytic residue at P224 (P = 0.0131);.;
MVP		0.15
MPC		0.46
ClinPred		0.19	T
GERP RS		2.1
Varity_R		0.023
gMVP		0.050

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: rs768735296; hg19: chr17-4862840;