dbSNP rs762154828: SPAG16:p.His235Arg (chr2-213350587-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024532.5(SPAG16):c.704A>G(p.His235Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000207 in 1,452,704 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: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SPAG16
NM_024532.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.55

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3636953).

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.704A>G	p.His235Arg	missense	Exon 7 of 16	NP_078808.3
SPAG16	NR_047659.2		n.899A>G		non_coding_transcript_exon	Exon 9 of 18
SPAG16	NR_047660.2		n.605A>G		non_coding_transcript_exon	Exon 6 of 15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPAG16	ENST00000331683.10	TSL:1 MANE Select	c.704A>G	p.His235Arg	missense	Exon 7 of 16	ENSP00000332592.5	Q8N0X2-1
SPAG16	ENST00000447990.1	TSL:1	c.704A>G	p.His235Arg	missense	Exon 7 of 10	ENSP00000400847.1	E7EWV3
SPAG16	ENST00000406979.6	TSL:1	n.*705A>G		non_coding_transcript_exon	Exon 9 of 18	ENSP00000385496.2	F8WB32

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000411

AC:

AN:

243584

AF XY:

0.00000759

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1452704

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722476

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32970

American (AMR)

AF:

0.00

AC:

AN:

42298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25840

East Asian (EAS)

AF:

0.00

AC:

AN:

39384

South Asian (SAS)

AF:

0.00

AC:

AN:

83928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53226

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1109310

Other (OTH)

AF:

0.00

AC:

AN:

60024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

ExAC

AF:

0.00000824

AC:

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

Benign

0.092

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.74

M_CAP

Benign

0.019

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.4

PhyloP100

5.6

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.7

REVEL

Benign

0.17

Sift

Uncertain

0.021

Sift4G

Uncertain

0.018

Polyphen

0.72

Vest4

0.44

MutPred

0.51

Gain of MoRF binding (P = 0.0078)

MVP

0.79

MPC

0.025

ClinPred

0.57

GERP RS

5.3

Varity_R

0.12

gMVP

0.066

Mutation Taster

=93/7

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over