dbSNP rs484870: SAXO5:p.Asp256Gly (chr19-7504396-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198534.3(SAXO5):c.767A>G(p.Asp256Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,613,120 control chromosomes in the GnomAD database, including 110,227 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.39 ( 11734 hom., cov: 31)

Exomes 𝑓: 0.36 ( 98493 hom. )

Consequence

SAXO5
NM_198534.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0720

Variant links:

Genes affected

SAXO5 (HGNC:24745): (stabilizer of axonemal microtubules 5)

SAXO5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6954541E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SAXO5	NM_198534.3 link	c.767A>G	p.Asp256Gly	missense_variant	Exon 4 of 9	ENST00000361664.7	NP_940936.2	Q8NA69

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TEX45	ENST00000361664.7 link	c.767A>G	p.Asp256Gly	missense_variant	Exon 4 of 9	1	NM_198534.3	ENSP00000355241.2	Q8NA69
TEX45	ENST00000596524.1 link	n.231+172A>G		intron_variant	Intron 2 of 3	4		ENSP00000471316.1	M0R0L7
TEX45	ENST00000596132.5 link	c.*183A>G		downstream_gene_variant		5		ENSP00000469882.1	M0QYK1

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58478

AN:

151854

Hom.:

11716

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.376

GnomAD3 exomes

AF:

0.347

AC:

87110

AN:

251194

Hom.:

15818

AF XY:

0.342

AC XY:

46495

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.466

Gnomad AMR exome

AF:

0.373

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.148

Gnomad SAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.355

Gnomad NFE exome

AF:

0.368

Gnomad OTH exome

AF:

0.352

GnomAD4 exome

AF:

0.364

AC:

531490

AN:

1461150

Hom.:

98493

Cov.:

AF XY:

0.360

AC XY:

261496

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.470

Gnomad4 AMR exome

AF:

0.370

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.200

Gnomad4 SAS exome

AF:

0.274

Gnomad4 FIN exome

AF:

0.355

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.363

GnomAD4 genome

AF:

0.385

AC:

58540

AN:

151970

Hom.:

11734

Cov.:

AF XY:

0.379

AC XY:

28154

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.471

Gnomad4 AMR

AF:

0.367

Gnomad4 ASJ

AF:

0.383

Gnomad4 EAS

AF:

0.160

Gnomad4 SAS

AF:

0.274

Gnomad4 FIN

AF:

0.353

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.375

Alfa

AF:

0.364

Hom.:

25375

Bravo

AF:

0.391

ESP6500AA

AF:

0.473

AC:

2082

ESP6500EA

AF:

0.375

AC:

3228

ExAC

AF:

0.349

AC:

42366

Asia WGS

AF:

0.258

AC:

901

AN:

3478

EpiCase

AF:

0.358

EpiControl

AF:

0.360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.5

DANN

Benign

0.17

DEOGEN2

Benign

0.0015

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00091

LIST_S2

Benign

0.25

MetaRNN

Benign

0.00017

MetaSVM

Benign

-0.96

PROVEAN

Benign

1.4

REVEL

Benign

0.024

Sift

Benign

0.95

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.031

MPC

0.27

ClinPred

0.0015

GERP RS

-1.8

Varity_R

0.042

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over