2-99035324-T-A

Position:

• chr2-99035324-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000393483.8(TSGA10):​c.1520A>T​(p.Asp507Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSGA10 ENST00000393483.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.44

Genes affected

TSGA10 (HGNC:14927): (testis specific 10) Predicted to enable structural molecule activity. Predicted to be involved in spermatogenesis. Predicted to act upstream of or within cell projection assembly. Predicted to be located in neuron projection; sperm fibrous sheath; and sperm principal piece. Implicated in spermatogenic failure 26. [provided by Alliance of Genome Resources, Apr 2022]

TSGA10 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSGA10	NM_025244.4	c.1520A>T	p.Asp507Val	missense_variant	17/21	ENST00000393483.8	NP_079520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSGA10	ENST00000393483.8	c.1520A>T	p.Asp507Val	missense_variant	17/21	1	NM_025244.4	ENSP00000377123.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jun 17, 2024

The c.1520A>T (p.D507V) alteration is located in exon 17 (coding exon 12) of the TSGA10 gene. This alteration results from a A to T substitution at nucleotide position 1520, causing the aspartic acid (D) at amino acid position 507 to be replaced by a valine (V). 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	0.77
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T;T;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	.;.;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.56	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-7.6	D;D;D;D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.022	D;D;D;.
Polyphen		1.0	D;D;D;.
Vest4		0.90
MutPred		0.17		Loss of disorder (P = 0.0436);Loss of disorder (P = 0.0436);Loss of disorder (P = 0.0436);Loss of disorder (P = 0.0436);
MVP		0.49
MPC		0.67
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.88
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr2-99651787;