7-130671678-C-T

Variant summary

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

The NM_052933.4(TSGA13):c.641G>A(p.Arg214Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000832 in 1,442,978 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: TSGA13 NM_052933.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.113

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=0.07176533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TSGA13	NM_052933.4	c.641G>A	p.Arg214Lys	missense_variant	7/8	ENST00000356588.8
TSGA13	NM_001304968.2	c.641G>A	p.Arg214Lys	missense_variant	8/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TSGA13	ENST00000356588.8	c.641G>A	p.Arg214Lys	missense_variant	7/8	1	NM_052933.4	P1
TSGA13	ENST00000456951.5	c.641G>A	p.Arg214Lys	missense_variant	8/9	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000162 AC: 4 AN: 246354 Hom.: 0 AF XY: 0.0000150 AC XY: 2 AN XY: 133400

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000225

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000832 AC: 12 AN: 1442978 Hom.: 0 Cov.: 31 AF XY: 0.00000418 AC XY: 3 AN XY: 718156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000282

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Dec 21, 2022

The c.641G>A (p.R214K) alteration is located in exon 7 (coding exon 6) of the TSGA13 gene. This alteration results from a G to A substitution at nucleotide position 641, causing the arginine (R) at amino acid position 214 to be replaced by a lysine (K). 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	0.10
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	5.1
Dann	Benign	0.90
DEOGEN2	Benign	0.088	T;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.026	N
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.023
Sift	Benign	0.12	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.0080	B;B
Vest4		0.24
MutPred		0.26		Gain of methylation at R214 (P = 0.0026);Gain of methylation at R214 (P = 0.0026);
MVP		0.20
MPC		0.15
ClinPred		0.028	T
GERP RS		2.4
Varity_R		0.11
gMVP		0.12

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: rs782262457; hg19: chr7-130356518;