NM_198534.3:c.767A>G

Variant names:

• chr19-7504396-A-G
• rs484870
• NM_198534.3:c.767A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (11734 hom., cov: 31)
  • Exomes 𝑓: 0.36 (98493 hom.)
• Consequence: SAXO5 NM_198534.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 29 publications found

Genes affected

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198534.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAXO5	NM_198534.3	MANE Select	c.767A>G	p.Asp256Gly	missense	Exon 4 of 9	NP_940936.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAXO5	ENST00000361664.7	TSL:1 MANE Select	c.767A>G	p.Asp256Gly	missense	Exon 4 of 9	ENSP00000355241.2
	SAXO5	ENST00000596524.1	TSL:4	n.231+172A>G		intron	N/A	ENSP00000471316.1
	SAXO5	ENST00000596132.5	TSL:5	c.*183A>G		downstream_gene	N/A	ENSP00000469882.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58478 AN: 151854 Hom.: 11716 Cov.: 31

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

GnomAD2 exomes AF: 0.347 AC: 87110 AN: 251194 AF XY: 0.342

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 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.: 37 AF XY: 0.360 AC XY: 261496 AN XY: 726910

African (AFR) AF: 0.470 AC: 15735 AN: 33472

American (AMR) AF: 0.370 AC: 16535 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 10113 AN: 26130

East Asian (EAS) AF: 0.200 AC: 7955 AN: 39692

South Asian (SAS) AF: 0.274 AC: 23672 AN: 86240

European-Finnish (FIN) AF: 0.355 AC: 18957 AN: 53416

Middle Eastern (MID) AF: 0.305 AC: 1756 AN: 5754

European-Non Finnish (NFE) AF: 0.373 AC: 414844 AN: 1111380

Other (OTH) AF: 0.363 AC: 21923 AN: 60362

GnomAD4 genome AF: 0.385 AC: 58540 AN: 151970 Hom.: 11734 Cov.: 31 AF XY: 0.379 AC XY: 28154 AN XY: 74288

African (AFR) AF: 0.471 AC: 19512 AN: 41470

American (AMR) AF: 0.367 AC: 5600 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1330 AN: 3470

East Asian (EAS) AF: 0.160 AC: 826 AN: 5162

South Asian (SAS) AF: 0.274 AC: 1318 AN: 4814

European-Finnish (FIN) AF: 0.353 AC: 3721 AN: 10542

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25089 AN: 67942

Other (OTH) AF: 0.375 AC: 787 AN: 2098

Alfa AF: 0.369 Hom.: 36501

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.5
DANN	Benign	0.17
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00091	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.00017	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.072
PROVEAN	Benign	1.4	N
REVEL	Benign	0.024
Sift	Benign	0.95	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.031
MPC		0.27
ClinPred		0.0015	T
GERP RS		-1.8
Varity_R		0.042
gMVP		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs484870; hg19: chr19-7569282; COSMIC: COSV64462596; COSMIC: COSV64462596;