chr7-130669028-T-G

Position:

• chr7-130669028-T-G

Variant summary

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

The NM_052933.4(TSGA13):​c.814A>C​(p.Thr272Pro) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TSGA13 NM_052933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.53

Genes affected

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

(HGNC:):

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=0.099401385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSGA13	NM_052933.4	c.814A>C	p.Thr272Pro	missense_variant	8/8	ENST00000356588.8
TSGA13	NM_001304968.2	c.814A>C	p.Thr272Pro	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSGA13	ENST00000356588.8	c.814A>C	p.Thr272Pro	missense_variant	8/8	1	NM_052933.4	P1
	ENST00000667779.1	n.177T>G		non_coding_transcript_exon_variant	1/1
TSGA13	ENST00000456951.5	c.814A>C	p.Thr272Pro	missense_variant	9/9	2		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Nov 08, 2022

The c.814A>C (p.T272P) alteration is located in exon 8 (coding exon 7) of the TSGA13 gene. This alteration results from a A to C substitution at nucleotide position 814, causing the threonine (T) at amino acid position 272 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	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Benign	0.079	T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.28	.;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.042	D;D
Polyphen		0.80	P;P
Vest4		0.21
MutPred		0.23		Loss of phosphorylation at T272 (P = 0.0624);Loss of phosphorylation at T272 (P = 0.0624);
MVP		0.014
MPC		0.43
ClinPred		0.66	D
GERP RS		-4.3
Varity_R		0.36
gMVP		0.50

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: rs1584626861; hg19: chr7-130353868;