7-130672861-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052933.4(TSGA13):c.403C>T(p.His135Tyr) 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. 14/20 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)
• Consequence: TSGA13 NM_052933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

Genes affected

TSGA13 (HGNC:12369): (testis specific 13)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13344786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSGA13	NM_052933.4	c.403C>T	p.His135Tyr	missense_variant	6/8	ENST00000356588.8
TSGA13	NM_001304968.2	c.403C>T	p.His135Tyr	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSGA13	ENST00000356588.8	c.403C>T	p.His135Tyr	missense_variant	6/8	1	NM_052933.4	P1
TSGA13	ENST00000456951.5	c.403C>T	p.His135Tyr	missense_variant	7/9	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 30, 2022

The c.403C>T (p.H135Y) alteration is located in exon 6 (coding exon 5) of the TSGA13 gene. This alteration results from a C to T substitution at nucleotide position 403, causing the histidine (H) at amino acid position 135 to be replaced by a tyrosine (Y). 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	0.099
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	13
Dann	Benign	0.68
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.061	N
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Benign	0.11
Sift	Benign	0.53	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.78	P;P
Vest4		0.29
MutPred		0.17		Gain of phosphorylation at H135 (P = 0.0181);Gain of phosphorylation at H135 (P = 0.0181);
MVP		0.26
MPC		0.22
ClinPred		0.63	D
GERP RS		3.4
Varity_R		0.099
gMVP		0.078

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: chr7-130357701;