Genetic Variant NM_004890.3:c.673C>T (chr17-4959545-G-A) – ACMG Classification: Likely_benign (-4 pts)

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.523

Publications

0 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.673C>T	p.Pro225Ser	missense_variant	Exon 7 of 7	ENST00000206020.8	NP_004881.2	O75391

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG7	ENST00000206020.8 link	c.673C>T	p.Pro225Ser	missense_variant	Exon 7 of 7	1	NM_004890.3	ENSP00000206020.3		O75391

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

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:

AN:

249078

AF XY:

0.0000592

show subpopulations

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:

AN:

1460836

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726748

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.000268

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111808

Other (OTH)

AF:

0.00

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000263

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41438

American (AMR)

AF:

0.00262

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000223

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

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

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0097

T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.69

N;.

PhyloP100

0.52

PrimateAI

Benign

0.34

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

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

(source)

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

Publications

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NM_004890.3:c.673C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over