dbSNP rs746520395: SAXO2:p.Arg200Ser (chr15-82282283-C-A) – 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_001348699.2(SAXO2):c.598C>A(p.Arg200Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R200C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SAXO2
NM_001348699.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.551

Publications

0 publications found

Variant links:

Genes affected

SAXO2 (HGNC:33727): (stabilizer of axonemal microtubules 2) Predicted to enable microtubule binding activity. Predicted to be involved in microtubule anchoring. Predicted to be active in microtubule cytoskeleton; nucleus; and sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

SAXO2 links:

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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=0.05798942).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348699.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAXO2	NM_001348699.2	MANE Select	c.598C>A	p.Arg200Ser	missense	Exon 4 of 4	NP_001335628.1	A0A804HKW2
SAXO2	NM_001348700.2		c.457C>A	p.Arg153Ser	missense	Exon 4 of 4	NP_001335629.1
SAXO2	NM_001348701.2		c.457C>A	p.Arg153Ser	missense	Exon 5 of 5	NP_001335630.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SAXO2	ENST00000682753.1	MANE Select	c.598C>A	p.Arg200Ser	missense	Exon 4 of 4	ENSP00000508095.1	A0A804HKW2
SAXO2	ENST00000339465.5	TSL:1	c.418C>A	p.Arg140Ser	missense	Exon 3 of 3	ENSP00000340445.5	Q658L1-1
SAXO2	ENST00000565501.1	TSL:1	n.709C>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

5.6

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.018

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.51

M_CAP

Benign

0.0028

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

PhyloP100

0.55

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.2

REVEL

Benign

0.046

Sift

Benign

0.14

Sift4G

Benign

0.44

Polyphen

0.64

Vest4

0.064

MutPred

0.45

Loss of MoRF binding (P = 0.0258)

MVP

0.061

MPC

0.10

ClinPred

0.23

GERP RS

0.34

Varity_R

0.096

gMVP

0.26

Mutation Taster

=95/5

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

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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