7-130669100-G-A

Position:

• chr7-130669100-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.742C>T​(p.Pro248Ser) 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. 12/20 in silico tools predict a benign outcome for this variant. 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.12

Genes affected

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

ENSG00000287547 (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=0.23072046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSGA13	NM_052933.4	c.742C>T	p.Pro248Ser	missense_variant	8/8	ENST00000356588.8	NP_443165.1
TSGA13	NM_001304968.2	c.742C>T	p.Pro248Ser	missense_variant	9/9		NP_001291897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSGA13	ENST00000356588.8	c.742C>T	p.Pro248Ser	missense_variant	8/8	1	NM_052933.4	ENSP00000348996.3
TSGA13	ENST00000456951.5	c.742C>T	p.Pro248Ser	missense_variant	9/9	2		ENSP00000406047.1
ENSG00000287547	ENST00000667779.1	n.249G>A		non_coding_transcript_exon_variant	1/1

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 01, 2024

The c.742C>T (p.P248S) alteration is located in exon 8 (coding exon 7) of the TSGA13 gene. This alteration results from a C to T substitution at nucleotide position 742, causing the proline (P) at amino acid position 248 to be replaced by a serine (S). 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	0.32
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-0.030
Eigen_PC	Benign	-0.027
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.61	.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Benign	0.064
Sift	Benign	0.046	D;D
Sift4G	Benign	0.093	T;T
Polyphen		0.73	P;P
Vest4		0.17
MutPred		0.23		Gain of phosphorylation at P248 (P = 0.036);Gain of phosphorylation at P248 (P = 0.036);
MVP		0.11
MPC		0.43
ClinPred		0.91	D
GERP RS		4.6
Varity_R		0.14
gMVP		0.17

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: chr7-130353940;