8-97276760-G-A

Variant names:

• chr8-97276760-G-A
• NM_033512.3:c.1085C>T

Variant summary

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

The NM_033512.3(TSPYL5):​c.1085C>T​(p.Ser362Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSPYL5 NM_033512.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.32

Genes affected

TSPYL5 (HGNC:29367): (TSPY like 5) Predicted to enable chromatin binding activity and histone binding activity. Involved in several processes, including cellular response to gamma radiation; positive regulation of protein kinase B signaling; and positive regulation of protein ubiquitination. Predicted to be active in chromatin and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC101927066 (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=0.26758122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL5	NM_033512.3	c.1085C>T	p.Ser362Phe	missense_variant	Exon 1 of 1	ENST00000322128.5	NP_277047.2
LOC101927066	NR_125390.1	n.471+142310C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPYL5	ENST00000322128.5	c.1085C>T	p.Ser362Phe	missense_variant	Exon 1 of 1	6	NM_033512.3	ENSP00000322802.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1085C>T (p.S362F) alteration is located in exon 1 (coding exon 1) of the TSPYL5 gene. This alteration results from a C to T substitution at nucleotide position 1085, causing the serine (S) at amino acid position 362 to be replaced by a phenylalanine (F). 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	Pathogenic	0.65
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.19
Sift	Benign	0.31	T
Sift4G	Benign	0.23	T
Polyphen		0.98	D
Vest4		0.30
MutPred		0.58		Loss of disorder (P = 0.0063);
MVP		0.19
MPC		1.7
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.39
gMVP		0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-98288988;