Genetic Variant NM_001348699.2:c.236C>T (chr15-82271605-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001348699.2(SAXO2):c.236C>T(p.Ser79Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000237 in 1,602,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SAXO2
NM_001348699.2 missense, splice_region

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.39

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18477032).

BP6

Variant 15-82271605-C-T is Benign according to our data. Variant chr15-82271605-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3792674.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAXO2	NM_001348699.2 link	c.236C>T	p.Ser79Leu	missense_variant, splice_region_variant	Exon 3 of 4	ENST00000682753.1	NP_001335628.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SAXO2	ENST00000682753.1 link	c.236C>T	p.Ser79Leu	missense_variant, splice_region_variant	Exon 3 of 4		NM_001348699.2	ENSP00000508095.1	A0A804HKW2
SAXO2	ENST00000339465.5 link	c.56C>T	p.Ser19Leu	missense_variant, splice_region_variant	Exon 2 of 3	1		ENSP00000340445.5	Q658L1-1
SAXO2	ENST00000565501.1 link	n.347C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 3	1
SAXO2	ENST00000565432.1 link	c.95C>T	p.Ser32Leu	missense_variant, splice_region_variant	Exon 4 of 4	4		ENSP00000458067.1	H3BVD4

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000247

AC:

AN:

243040

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

131232

show subpopulations

Gnomad AFR exome

AF:

0.000187

Gnomad AMR exome

AF:

0.0000307

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:

0.00000899

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1450560

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

721244

show subpopulations

Gnomad4 AFR exome

AF:

0.000182

Gnomad4 AMR exome

AF:

0.0000235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000163

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000254

Hom.:

Bravo

AF:

0.000102

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 03, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-0.0059

Eigen_PC

Benign

-0.037

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.6

N;D

REVEL

Benign

0.24

Sift

Uncertain

0.020

D;T

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.99

D;.

Vest4

0.19

MVP

0.44

MPC

0.086

ClinPred

0.21

GERP RS

3.1

Varity_R

0.088

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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