15-82271650-C-T

Variant names:

• chr15-82271650-C-T
• rs16973457
• NM_001348699.2:c.281C>T

Variant summary

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

The NM_001348699.2(SAXO2):​c.281C>T​(p.Pro94Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,612,380 control chromosomes in the GnomAD database, including 194,539 homozygotes. In-silico tool predicts 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. P94R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.44 (15319 hom., cov: 32)
  • Exomes 𝑓: 0.49 (179220 hom.)
• Consequence: SAXO2 NM_001348699.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92
• Publications: 40 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015205145).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAXO2	NM_001348699.2	MANE Select	c.281C>T	p.Pro94Leu	missense	Exon 3 of 4	NP_001335628.1
	SAXO2	NM_001348700.2		c.140C>T	p.Pro47Leu	missense	Exon 3 of 4	NP_001335629.1
	SAXO2	NM_001348701.2		c.140C>T	p.Pro47Leu	missense	Exon 4 of 5	NP_001335630.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAXO2	ENST00000682753.1	MANE Select	c.281C>T	p.Pro94Leu	missense	Exon 3 of 4	ENSP00000508095.1
	SAXO2	ENST00000339465.5	TSL:1	c.101C>T	p.Pro34Leu	missense	Exon 2 of 3	ENSP00000340445.5
	SAXO2	ENST00000565501.1	TSL:1	n.392C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66649 AN: 151872 Hom.: 15309 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.459

GnomAD2 exomes AF: 0.439 AC: 110245 AN: 251040 AF XY: 0.454

Gnomad AFR exome AF: 0.344

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.606

Gnomad EAS exome AF: 0.211

Gnomad FIN exome AF: 0.486

Gnomad NFE exome AF: 0.510

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.489 AC: 714808 AN: 1460390 Hom.: 179220 Cov.: 42 AF XY: 0.491 AC XY: 356921 AN XY: 726582

African (AFR) AF: 0.340 AC: 11378 AN: 33456

American (AMR) AF: 0.250 AC: 11178 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 15887 AN: 26120

East Asian (EAS) AF: 0.254 AC: 10078 AN: 39682

South Asian (SAS) AF: 0.501 AC: 43164 AN: 86184

European-Finnish (FIN) AF: 0.487 AC: 26019 AN: 53406

Middle Eastern (MID) AF: 0.536 AC: 3093 AN: 5766

European-Non Finnish (NFE) AF: 0.508 AC: 564760 AN: 1110744

Other (OTH) AF: 0.485 AC: 29251 AN: 60342

GnomAD4 genome AF: 0.439 AC: 66680 AN: 151990 Hom.: 15319 Cov.: 32 AF XY: 0.434 AC XY: 32206 AN XY: 74270

African (AFR) AF: 0.351 AC: 14554 AN: 41444

American (AMR) AF: 0.342 AC: 5231 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2071 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1072 AN: 5168

South Asian (SAS) AF: 0.494 AC: 2379 AN: 4812

European-Finnish (FIN) AF: 0.472 AC: 4978 AN: 10544

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.514 AC: 34933 AN: 67962

Other (OTH) AF: 0.455 AC: 961 AN: 2112

Alfa AF: 0.486 Hom.: 49168

Bravo AF: 0.419

TwinsUK AF: 0.512 AC: 1900

ALSPAC AF: 0.523 AC: 2014

ESP6500AA AF: 0.360 AC: 1585

ESP6500EA AF: 0.515 AC: 4433

ExAC AF: 0.447 AC: 54240

Asia WGS AF: 0.322 AC: 1122 AN: 3478

EpiCase AF: 0.513

EpiControl AF: 0.516

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.89	D
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.91	T
PhyloP100		2.9
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.13
Sift	Benign	0.091	T
Sift4G	Benign	0.12	T
Polyphen		0.87	P
Vest4		0.20
MPC		0.38
ClinPred		0.044	T
GERP RS		3.9
Varity_R		0.083
gMVP		0.35
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16973457; hg19: chr15-82563991; COSMIC: COSV59754947;