19-7504396-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000361664.7(SAXO5):​c.767A>T​(p.Asp256Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SAXO5 ENST00000361664.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361664.7. 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>T	p.Asp256Val	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>T	p.Asp256Val	missense	Exon 4 of 9	ENSP00000355241.2
	SAXO5	ENST00000596524.1	TSL:4	n.231+172A>T		intron	N/A	ENSP00000471316.1
	SAXO5	ENST00000596132.5	TSL:5	c.*183A>T		downstream_gene	N/A	ENSP00000469882.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461750 Hom.: 0 Cov.: 37 AF XY: 0.00000413 AC XY: 3 AN XY: 727180

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

American (AMR) AF: 0.00 AC: 0 AN: 44708

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111920

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.58
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.072
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.012
Sift	Benign	0.055	T
Sift4G	Benign	0.14	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.27		Loss of solvent accessibility (P = 0.0098)
MVP		0.15
MPC		0.29
ClinPred		0.058	T
GERP RS		-1.8
Varity_R		0.10
gMVP		0.34
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.33		Position offset: -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;