15-56383973-T-C

Position:

• chr15-56383973-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395496.1(TEX9):​c.205T>C​(p.Ser69Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,460,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TEX9 NM_001395496.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.667

Genes affected

TEX9 (HGNC:29585): (testis expressed 9)

TEX9 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2758244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX9	NM_001395496.1	c.205T>C	p.Ser69Pro	missense_variant	4/12	ENST00000696102.1	NP_001382425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX9	ENST00000696102.1	c.205T>C	p.Ser69Pro	missense_variant	4/12		NM_001395496.1	ENSP00000512397.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000799 AC: 2 AN: 250274 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135268

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1460316 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 726368

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

The c.205T>C (p.S69P) alteration is located in exon 4 (coding exon 4) of the TEX9 gene. This alteration results from a T to C substitution at nucleotide position 205, causing the serine (S) at amino acid position 69 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.11
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.99	D;.
Vest4		0.56
MVP		0.067
MPC		0.064
ClinPred		0.87	D
GERP RS		0.12
Varity_R		0.31
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs147433159; hg19: chr15-56676171;