17-4959545-G-T

Variant names:

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

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>A​(p.Pro225Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,836 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• 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=0.039137542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG7	NM_004890.3	c.673C>A	p.Pro225Thr	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>A	p.Pro225Thr	missense_variant	Exon 7 of 7	1	NM_004890.3	ENSP00000206020.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460836 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726748

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5612

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111808

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.84
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.14	N;.
PhyloP100		0.52
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.47	N;.
REVEL	Benign	0.17
Sift	Benign	0.99	T;.
Sift4G	Uncertain	0.040	D;T
Polyphen		0.11	B;.
Vest4		0.098
MutPred		0.14		Gain of phosphorylation at P225 (P = 0.0183);.;
MVP		0.13
MPC		0.53
ClinPred		0.081	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.060
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: rs768735296; hg19: chr17-4862840;