chr15-82282319-C-T

Variant names:

• chr15-82282319-C-T
• rs550515297
• NM_001348699.2:c.634C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001348699.2(SAXO2):​c.634C>T​(p.Arg212Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: SAXO2 NM_001348699.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3518718).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAXO2	NM_001348699.2	MANE Select	c.634C>T	p.Arg212Cys	missense	Exon 4 of 4	NP_001335628.1	A0A804HKW2
	SAXO2	NM_001348700.2		c.493C>T	p.Arg165Cys	missense	Exon 4 of 4	NP_001335629.1
	SAXO2	NM_001348701.2		c.493C>T	p.Arg165Cys	missense	Exon 5 of 5	NP_001335630.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAXO2	ENST00000682753.1	MANE Select	c.634C>T	p.Arg212Cys	missense	Exon 4 of 4	ENSP00000508095.1	A0A804HKW2
	SAXO2	ENST00000339465.5	TSL:1	c.454C>T	p.Arg152Cys	missense	Exon 3 of 3	ENSP00000340445.5	Q658L1-1
	SAXO2	ENST00000565501.1	TSL:1	n.745C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000795 AC: 20 AN: 251450 AF XY: 0.0000883

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000547 AC: 80 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.0000688 AC XY: 50 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000487 AC: 42 AN: 86256

European-Finnish (FIN) AF: 0.000337 AC: 18 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1112006

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74444

African (AFR) AF: 0.00 AC: 0 AN: 41552

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4812

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000676 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000988 AC: 12

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.74	T
PhyloP100		1.6
PrimateAI	Uncertain	0.48	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.33
MutPred		0.68		Loss of disorder (P = 0.0495)
MVP		0.52
MPC		0.54
ClinPred		0.76	D
GERP RS		3.9
Varity_R		0.31
gMVP		0.51
Mutation Taster		=66/34	polymorphism

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: rs550515297; hg19: chr15-82574660; COSMIC: COSV100255909;