Genetic Variant SPAG16:p.Arg192Cys (chr2-213340200-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024532.5(SPAG16):c.574C>T(p.Arg192Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000138 in 1,611,238 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

SPAG16
NM_024532.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.61

Publications

1 publications found

Variant links:

Genes affected

SPAG16 (HGNC:23225): (sperm associated antigen 16) Cilia and flagella are comprised of a microtubular backbone, the axoneme, which is organized by the basal body and surrounded by plasma membrane. SPAG16 encodes 2 major proteins that associate with the axoneme of sperm tail and the nucleus of postmeiotic germ cells, respectively (Zhang et al., 2007 [PubMed 17699735]).[supplied by OMIM, Jul 2008]

SPAG16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03172636).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024532.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SPAG16	NM_024532.5	MANE Select	c.574C>T	p.Arg192Cys	missense	Exon 6 of 16	NP_078808.3
SPAG16	NR_047659.2		n.769C>T		non_coding_transcript_exon	Exon 8 of 18
SPAG16	NR_047660.2		n.475C>T		non_coding_transcript_exon	Exon 5 of 15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPAG16	ENST00000331683.10	TSL:1 MANE Select	c.574C>T	p.Arg192Cys	missense	Exon 6 of 16	ENSP00000332592.5	Q8N0X2-1
SPAG16	ENST00000447990.1	TSL:1	c.574C>T	p.Arg192Cys	missense	Exon 6 of 10	ENSP00000400847.1	E7EWV3
SPAG16	ENST00000406979.6	TSL:1	n.*575C>T		non_coding_transcript_exon	Exon 8 of 18	ENSP00000385496.2	F8WB32

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

151692

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00462

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000233

AC:

AN:

248522

AF XY:

0.000268

show subpopulations

Gnomad AFR exome

AF:

0.0000624

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00501

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000136

AC:

198

AN:

1459428

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

118

AN XY:

725922

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33354

American (AMR)

AF:

0.00

AC:

AN:

44288

Ashkenazi Jewish (ASJ)

AF:

0.00514

AC:

134

AN:

26068

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39536

South Asian (SAS)

AF:

0.00

AC:

AN:

85828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000387

AC:

AN:

1110940

Other (OTH)

AF:

0.000332

AC:

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000158

AC:

AN:

151810

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41384

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00462

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67924

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000281

Hom.:

Bravo

AF:

0.000178

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000594

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.072

MetaRNN

Benign

0.032

MetaSVM

Uncertain

-0.054

MutationAssessor

Uncertain

2.6

PhyloP100

3.6

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-7.1

REVEL

Uncertain

0.34

Sift

Uncertain

0.011

Sift4G

Uncertain

0.048

Polyphen

0.63

Vest4

0.67

MVP

0.89

MPC

0.18

ClinPred

0.64

GERP RS

5.1

Varity_R

0.71

gMVP

0.53

Mutation Taster

=82/18

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over