Genetic Variant SPAG11A:p.Arg55Cys (chr8-7848792-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001395484.1(SPAG11A):c.163C>T(p.Arg55Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 11)

Exomes 𝑓: 0.00016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SPAG11A
NM_001395484.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.224

Variant links:

Genes affected

SPAG11A (HGNC:33342): (sperm associated antigen 11A) Involved in antimicrobial humoral immune response mediated by antimicrobial peptide and cytolysis by host of symbiont cells. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SPAG11A links:

LOC124901865 (HGNC:):

LOC124901865 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03257653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG11A	NM_001395484.1 link	c.163C>T	p.Arg55Cys	missense_variant	Exon 2 of 3	ENST00000642566.2	NP_001382413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG11A	ENST00000642566.2 link	c.163C>T	p.Arg55Cys	missense_variant	Exon 2 of 3		NM_001395484.1	ENSP00000496500.1		A0A2R8Y853

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

108

AN:

92828

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00341

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00373

Gnomad NFE

AF:

0.000166

Gnomad OTH

AF:

0.00180

GnomAD3 exomes

AF:

0.000228

AC:

AN:

70204

Hom.:

AF XY:

0.000142

AC XY:

AN XY:

35194

show subpopulations

Gnomad AFR exome

AF:

0.00202

Gnomad AMR exome

AF:

0.000152

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000159

AC:

118

AN:

741800

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

378836

show subpopulations

Gnomad4 AFR exome

AF:

0.00251

Gnomad4 AMR exome

AF:

0.000145

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000318

Gnomad4 SAS exome

AF:

0.0000530

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000949

Gnomad4 OTH exome

AF:

0.0000842

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00116

AC:

108

AN:

92916

Hom.:

Cov.:

AF XY:

0.000879

AC XY:

AN XY:

43236

show subpopulations

Gnomad4 AFR

AF:

0.00340

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000166

Gnomad4 OTH

AF:

0.00178

Alfa

AF:

0.000612

Hom.:

ExAC

AF:

0.0000489

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.163C>T (p.R55C) alteration is located in exon 2 (coding exon 2) of the SPAG11A gene. This alteration results from a C to T substitution at nucleotide position 163, causing the arginine (R) at amino acid position 55 to be replaced by a cysteine (C). 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

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.014

LIST_S2

Uncertain

0.90

D;.;D;.;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.033

T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.0

.;.;.;.;L

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-4.9

D;D;.;D;D

REVEL

Benign

0.081

Sift

Uncertain

0.0040

D;D;.;D;D

Sift4G

Uncertain

0.0050

D;D;.;D;D

Vest4

0.20

MVP

0.28

MPC

2.6

ClinPred

0.096

GERP RS

0.090

gMVP

0.063

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over