17-4960038-T-C

Position:

• chr17-4960038-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004890.3(SPAG7):​c.401A>G​(p.Glu134Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SPAG7 NM_004890.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.15

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2683765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG7	NM_004890.3	c.401A>G	p.Glu134Gly	missense_variant	5/7	ENST00000206020.8	NP_004881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG7	ENST00000206020.8	c.401A>G	p.Glu134Gly	missense_variant	5/7	1	NM_004890.3	ENSP00000206020.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461838 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000613 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2021

The c.401A>G (p.E134G) alteration is located in exon 5 (coding exon 5) of the SPAG7 gene. This alteration results from a A to G substitution at nucleotide position 401, causing the glutamic acid (E) at amino acid position 134 to be replaced by a glycine (G). 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	0.18
BayesDel_addAF	Benign	-0.0058	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	T;T;T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-4.0	.;D;.
REVEL	Benign	0.21
Sift	Uncertain	0.0040	.;D;.
Sift4G	Benign	0.063	T;T;T
Polyphen		0.65	.;P;.
Vest4		0.46
MVP		0.25
MPC		0.84
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.37
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-4863333;