rs484870

chr19-7504396-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198534.3(TEX45):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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.39 (11734 hom., cov: 31)
  • Exomes 𝑓: 0.36 (98493 hom.)
• Consequence: TEX45 NM_198534.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

Genes affected

TEX45 (HGNC:):

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

ACMG classification

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/exons	MANE	UniProt
TEX45	NM_198534.3	c.767A>G	p.Asp256Gly	missense_variant	4/9	ENST00000361664.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SAXO5	ENST00000361664.7	c.767A>G	p.Asp256Gly	missense_variant	4/9	1	NM_198534.3	P1
SAXO5	ENST00000596524.1	c.231+172A>G		intron_variant, NMD_transcript_variant		4

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

GnomAD3 exomes AF: 0.347 AC: 87110 AN: 251194 Hom.: 15818 AF XY: 0.342 AC XY: 46495 AN XY: 135838

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

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.: 31 AF XY: 0.379 AC XY: 28154 AN XY: 74288

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	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
MutationTaster	Benign	1.0	P
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

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

Other links and lift over

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