rs768735296

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-4959545-G-A
• chr17-4959545-G-C
• chr17-4959545-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004890.3(SPAG7):​c.673C>T​(p.Pro225Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,012 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SPAG7 NM_004890.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015681833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG7	NM_004890.3	c.673C>T	p.Pro225Ser	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>T	p.Pro225Ser	missense_variant	Exon 7 of 7	1	NM_004890.3	ENSP00000206020.3

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000602 AC: 15 AN: 249078 AF XY: 0.0000592

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000377

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460836 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 726748

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

American (AMR) AF: 0.000268 AC: 12 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: 0.0000464 AC: 4 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 AF: 0.000263 AC: 40 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00262 AC: 40 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000223

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.673C>T (p.P225S) alteration is located in exon 7 (coding exon 7) of the SPAG7 gene. This alteration results from a C to T substitution at nucleotide position 673, causing the proline (P) at amino acid position 225 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.84
DEOGEN2	Benign	0.0097	T;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.016	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.69	N;.
PhyloP100		0.52
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.69	N;.
REVEL	Benign	0.21
Sift	Benign	0.64	T;.
Sift4G	Benign	0.22	T;T
Polyphen		0.0030	B;.
Vest4		0.076
MutPred		0.14		Gain of phosphorylation at P225 (P = 0.0092);.;
MVP		0.12
MPC		0.47
ClinPred		0.017	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.028
gMVP		0.054
Mutation Taster		=96/4	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;