7-130671786-A-T

Position:

• chr7-130671786-A-T

Variant summary

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

The NM_052933.4(TSGA13):​c.533T>A​(p.Phe178Tyr) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSGA13 NM_052933.4 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07

Genes affected

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

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
TSGA13	NM_052933.4	c.533T>A	p.Phe178Tyr	missense_variant, splice_region_variant	7/8	ENST00000356588.8	NP_443165.1
TSGA13	NM_001304968.2	c.533T>A	p.Phe178Tyr	missense_variant, splice_region_variant	8/9		NP_001291897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSGA13	ENST00000356588.8	c.533T>A	p.Phe178Tyr	missense_variant, splice_region_variant	7/8	1	NM_052933.4	ENSP00000348996.3
TSGA13	ENST00000456951.5	c.533T>A	p.Phe178Tyr	missense_variant, splice_region_variant	8/9	2		ENSP00000406047.1

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

Aug 20, 2024

The c.533T>A (p.F178Y) alteration is located in exon 7 (coding exon 6) of the TSGA13 gene. This alteration results from a T to A substitution at nucleotide position 533, causing the phenylalanine (F) at amino acid position 178 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	Uncertain	0.44
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.54	.;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		1.0	D;D
Vest4		0.81
MutPred		0.31		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.067
MPC		0.22
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.71
gMVP		0.29

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: chr7-130356626;