Genetic Variant SPAG11A:p.Arg79Lys (chr8-7860667-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001395484.1(SPAG11A):c.236G>A(p.Arg79Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,519,534 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00013 ( 2 hom., cov: 26)

Exomes 𝑓: 0.00015 ( 20 hom. )

Consequence

SPAG11A
NM_001395484.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.07

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.9960275E-4).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG11A	NM_001395484.1 link	c.236G>A	p.Arg79Lys	missense_variant	Exon 3 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.236G>A	p.Arg79Lys	missense_variant	Exon 3 of 3		NM_001395484.1	ENSP00000496500.1		A0A2R8Y853

Frequencies

GnomAD3 genomes

AF:

0.000134

AC:

AN:

134402

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00162

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000112

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000167

Gnomad OTH

AF:

0.000543

GnomAD2 exomes

AF:

0.000217

AC:

AN:

230648

AF XY:

0.000193

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000303

Gnomad ASJ exome

AF:

0.00206

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.000530

GnomAD4 exome

AF:

0.000145

AC:

201

AN:

1385132

Hom.:

Cov.:

AF XY:

0.000153

AC XY:

105

AN XY:

685568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32450

American (AMR)

AF:

0.0000235

AC:

AN:

42642

Ashkenazi Jewish (ASJ)

AF:

0.00238

AC:

AN:

23970

East Asian (EAS)

AF:

0.00

AC:

AN:

30560

South Asian (SAS)

AF:

0.0000402

AC:

AN:

74668

European-Finnish (FIN)

AF:

0.0000208

AC:

AN:

48144

Middle Eastern (MID)

AF:

0.000738

AC:

AN:

5420

European-Non Finnish (NFE)

AF:

0.000117

AC:

125

AN:

1070614

Other (OTH)

AF:

0.000176

AC:

AN:

56664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000134

AC:

AN:

134402

Hom.:

Cov.:

AF XY:

0.0000922

AC XY:

AN XY:

65092

show subpopulations

African (AFR)

AF:

0.0000257

AC:

AN:

38934

American (AMR)

AF:

0.00

AC:

AN:

13596

Ashkenazi Jewish (ASJ)

AF:

0.00162

AC:

AN:

3078

East Asian (EAS)

AF:

0.00

AC:

AN:

3462

South Asian (SAS)

AF:

0.00

AC:

AN:

3620

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

8968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.000167

AC:

AN:

59868

Other (OTH)

AF:

0.000543

AC:

AN:

1842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000629

Hom.:

ExAC

AF:

0.000207

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 15, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.236G>A (p.R79K) alteration is located in exon 3 (coding exon 3) of the SPAG11A gene. This alteration results from a G to A substitution at nucleotide position 236, causing the arginine (R) at amino acid position 79 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.092

.;.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.54

T;.;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.00030

T;T;T

MetaSVM

Benign

-0.99

PhyloP100

2.1

PROVEAN

Benign

-0.93

.;N;D

REVEL

Benign

0.21

Sift

Benign

0.40

.;T;T

Sift4G

Benign

0.45

.;T;D

Vest4

0.31, 0.41

MVP

0.014

MPC

0.013

ClinPred

0.062

GERP RS

2.3

gMVP

0.046

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over